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1
Moldvai, István, Eszter Gács-Baitz, and Csaba Szántay. "Chemistry of indoles carrying basic functions. I. Transformation of hydroxyindolones into indoles." Recueil des Travaux Chimiques des Pays-Bas 110, no. 11 (2010): 437–40. http://dx.doi.org/10.1002/recl.19911101102.
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MOLDVAI, I., E. GACS-BAITZ, and C. SZANTAY. "ChemInform Abstract: Chemistry of Indoles Carrying Basic Functions. Part 1. Transformation of Hydroxyindolones into Indoles." ChemInform 23, no. 14 (2010): no. http://dx.doi.org/10.1002/chin.199214194.
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Chang, Chieh-Yu, Yu-Huan Lin, and Yen-Ku Wu. "Palladium-catalyzed N1-selective allylation of indoles with allylic alcohols promoted by titanium tetraisopropoxide." Chemical Communications 55, no. 8 (2019): 1116–19. http://dx.doi.org/10.1039/c8cc09817d.
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Zhai, Yizhan, Xue Zhang, and Shengming Ma. "Stereoselective rhodium-catalyzed 2-C–H 1,3-dienylation of indoles: dual functions of the directing group." Chemical Science 12, no. 34 (2021): 11330–37. http://dx.doi.org/10.1039/d1sc02167b.
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A rhodium-catalyzed intermolecular highly stereoselective 1,3-dienylation at the 2-position of indoles with non-terminal allenyl carbonates has been developed by using 2-pyrimidinyl or pyridinyl as the directing group.
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Sz�tay, Csaba, Istv� Moldval, Csaba Sz�tay Jr., and Csaba Sz�tay. "Chemistry of Indoles Carrying Basic Functions. Part II. Synthesis of 4-Substituted Cyclohept[c.d]indoles. A New Entry into the Ring System." HETEROCYCLES 34, no. 2 (1992): 219. http://dx.doi.org/10.3987/com-91-5803.
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Vadaq, Nadira, Yue Zhang, Elise Meeder, et al. "Microbiome-Related Indole and Serotonin Metabolites are Linked to Inflammation and Psychiatric Symptoms in People Living with HIV." International Journal of Tryptophan Research 15 (January 2022): 117864692211268. http://dx.doi.org/10.1177/11786469221126888.
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Background: People living with HIV (PLHIV) exhibit dysregulation of tryptophan metabolism. Altered gut microbiome composition in PLHIV might be involved. Mechanistic consequences within the 3 major tryptophan metabolism pathways (serotonin, kynurenine, and indoles), and functional consequences for platelet, immune and behavioral functions are unknown. We investigated plasma tryptophan metabolites, gut microbiome composition, and their association with platelet function, inflammation, and psychiatric symptoms. Methods: This study included 211 PLHIV on long-term antiretroviral treatment (ART). Plasma tryptophan pathway metabolites were measured using time-of-flight mass spectrometry. Bacterial composition was profiled using metagenomic sequencing. Platelet reactivity and serotonin levels were quantified by flowcytometry and ELISA, respectively. Circulating inflammatory markers were determined using ELISA. Symptoms of depression and impulsivity were measured by DASS-42 and BIS-11 self-report questionnaires, respectively. Results: Plasma serotonin and indole metabolites were associated with gut bacterial composition. Notably, species enriched in PLHIV were associated with 3-methyldioxyindole. Platelet serotonin concentrations were elevated in PLHIV, without effects on platelet reactivity. Plasma serotonin and indole metabolites were positively associated with plasma IL-10 and TNF-α concentrations. Finally, higher tryptophan, serotonin, and indole metabolites were associated with lower depression and anxiety, whereas higher kynurenine metabolites were associated with increased impulsivity. Conclusion: Our results suggest that gut bacterial composition and dysbiosis in PLHIV on ART contribute to tryptophan metabolism, which may have clinical consequences for immune function and behavior.
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MOLDVAI, I., C. JUN SZANTAY, and C. SZANTAY. "ChemInform Abstract: Chemistry of Indoles Carrying Basic Functions. Part 2. Synthesis of 4- Substituted Cyclohept(c,d)indoles. A New Entry into the Ring System." ChemInform 23, no. 27 (2010): no. http://dx.doi.org/10.1002/chin.199227169.
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Bock, Karl Walter. "Human and rodent aryl hydrocarbon receptor (AHR): from mediator of dioxin toxicity to physiologic AHR functions and therapeutic options." Biological Chemistry 398, no. 4 (2017): 455–64. http://dx.doi.org/10.1515/hsz-2016-0303.
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Abstract Metabolism of aryl hydrocarbons and toxicity of dioxins led to the discovery of the aryl hydrocarbon receptor (AHR). Tremendous advances have been made on multiplicity of AHR signaling and identification of endogenous ligands including the tryptophan metabolites FICZ and kynurenine. However, human AHR functions are still poorly understood due to marked species differences as well as cell-type- and cell context-dependent AHR functions. Observations in dioxin-poisoned individuals may provide hints to physiologic AHR functions in humans. Based on these observations three human AHR functions are discussed: (1) Chemical defence and homeostasis of endobiotics. The AHR variant Val381 in modern humans leads to reduced AHR affinity to aryl hydrocarbons in comparison with Neanderthals and primates expressing the Ala381 variant while affinity to indoles remains unimpaired. (2) Homeostasis of stem/progenitor cells. Dioxins dysregulate homeostasis in sebocyte stem cells. (3) Modulation of immunity. In addition to microbial defence, AHR may be involved in a ‘disease tolerance defence pathway’. Further characterization of physiologic AHR functions may lead to therapeutic options.
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Duvauchelle, Valentin, David Bénimélis, Patrick Meffre та Zohra Benfodda. "Catalyst-Free Site Selective Hydroxyalkylation of 5-Phenylthiophen-2-amine with α-Trifluoromethyl Ketones through Electrophilic Aromatic Substitution". Molecules 27, № 3 (2022): 925. http://dx.doi.org/10.3390/molecules27030925.
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An original and effective approach for achieving trifluoromethyl hydroxyalkylation of 5-phenylthiophen-2-amine using α-trifluoromethyl ketones is described. In the last few years, reaction of Friedel-Crafts had been widely used to realize hydroxyalkylation on heterocycles such as indoles or thiophenes by means of Lewis acid as catalyst. Additionally, amine functions are rarely free when carbonyl reagents are used because of their tendency to form imines. This is the first time that a site-selective electrophilic aromatic substitution on C3 atom of an unprotected 5-phenylthiophen-2-amine moiety is reported. The liberty to allow reaction in neutral conditions between free amine is valuable in a synthesis pathway. The reaction proceeds smoothly using an atom-economical metal-and catalyst-free methodology in good to excellent yields. A mechanism similar to an electrophilic aromatic substitution has been proposed.
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Bershtein, L. M. "E. J. Pavlik, ed. Estrogens, progestins and their antagonists. - Vol. 2. Functions and mechanisms of action. - Boston, Basel, Berlin: Bikhauser, 1996 .-- 632 p." Problems of Endocrinology 44, no. 2 (2019): 53–54. http://dx.doi.org/10.14341/probl199844253-54.
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The book under review is part of a lengthy and interesting series for specialists, published by the Birkhauser Publishing House and having the common title Hormones in Normal and Pathological Conditions. The first volume of the book, a review of which is published in Issue 3 of the journal “Oncology Issues” for 1997, deals mainly with the degree of oncological risk of estrogen replacement therapy in menopause, about the not always unambiguous anticarcinogenic properties of phytoestrogens and food indoles, and about modern approaches to hormone therapy for prostate cancer, etc., i.e., mainly about the problems of oncological endocrinology. The 2nd volume of this publication, as its editor E. Pavlik writes in the introduction to the book, is devoted to the physiological and molecular mechanisms of action of estrogens, progestins and their antagonists, and is primarily focused on the discussion of the effect of various and often even opposite effects these compounds in different cells and tissues. A highly qualified team of authors, assembled by the editor, was able to ensure the implementation of this difficult and responsible task.
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Rizwan, Komal, Ismat Majeed, Muhammad Bilal, Tahir Rasheed, Ahmad Shakeel, and Shahid Iqbal. "Phytochemistry and Diverse Pharmacology of Genus Mimosa: A Review." Biomolecules 12, no. 1 (2022): 83. http://dx.doi.org/10.3390/biom12010083.
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The genus Mimosa belongs to the Fabaceae family and comprises almost 400 species of herbs, shrubs and ornamental trees. The genus Mimosa is found all over the tropics and subtropics of Asia, Africa, South America, North America and Australia. Traditionally, this genus has been popular for the treatment of jaundice, diarrhea, fever, toothache, wound healing, asthma, leprosy, vaginal and urinary complaints, skin diseases, piles, gastrointestinal disorders, small pox, hepatitis, tumor, HIV, ulcers and ringworm. The review covered literature available from 1959 to 2020 collected from books, scientific journals and electronic searches, such as Science Direct, Web of Science and Google scholar. Various keywords, such as Mimosa, secondary metabolites, medicines, phytochemicals and pharmacological values, were used for the data search. The Mimosa species are acknowledged to be an essential source of secondary metabolites with a wide-ranging biological functions, and up until now, 145 compounds have been isolated from this genus. Pharmacological studies showed that isolated compounds possess significant potential, such as antiprotozoal, antimicrobial, antiviral, antioxidant, and antiproliferative as well as cytotoxic activities. Alkaloids, chalcones, flavonoids, indoles, terpenes, terpenoids, saponins, steroids, amino acids, glycosides, flavanols, phenols, lignoids, polysaccharides, lignins, salts and fatty esters have been isolated from this genus. This review focused on the medicinal aspects of the Mimosa species and may provide a comprehensive understanding of the prospective of this genus as a foundation of medicine, supplement and nourishment. The plants of this genus could be a potential source of medicines in the near future.
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Bhargava, Shruti, Erik Merckelbach, Heidi Noels, Ashima Vohra, and Joachim Jankowski. "Homeostasis in the Gut Microbiota in Chronic Kidney Disease." Toxins 14, no. 10 (2022): 648. http://dx.doi.org/10.3390/toxins14100648.
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The gut microbiota consists of trillions of microorganisms, fulfilling important roles in metabolism, nutritional intake, physiology and maturation of the immune system, but also aiding and abetting the progression of chronic kidney disease (CKD). The human gut microbiome consists of bacterial species from five major bacterial phyla, namely Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, and Verrucomicrobia. Alterations in the members of these phyla alter the total gut microbiota, with a decline in the number of symbiotic flora and an increase in the pathogenic bacteria, causing or aggravating CKD. In addition, CKD-associated alteration of this intestinal microbiome results in metabolic changes and the accumulation of amines, indoles and phenols, among other uremic metabolites, which have a feedforward adverse effect on CKD patients, inhibiting renal functions and increasing comorbidities such as atherosclerosis and cardiovascular diseases (CVD). A classification of uremic toxins according to the degree of known toxicity based on the experimental evidence of their toxicity (number of systems affected) and overall experimental and clinical evidence was selected to identify the representative uremic toxins from small water-soluble compounds, protein-bound compounds and middle molecules and their relation to the gut microbiota was summarized. Gut-derived uremic metabolites accumulating in CKD patients further exhibit cell-damaging properties, damage the intestinal epithelial cell wall, increase gut permeability and lead to the translocation of bacteria and endotoxins from the gut into the circulatory system. Elevated levels of endotoxins lead to endotoxemia and inflammation, further accelerating CKD progression. In recent years, the role of the gut microbiome in CKD pathophysiology has emerged as an important aspect of corrective treatment; however, the mechanisms by which the gut microbiota contributes to CKD progression are still not completely understood. Therefore, this review summarizes the current state of research regarding CKD and the gut microbiota, alterations in the microbiome, uremic toxin production, and gut epithelial barrier degradation.
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Tang, Jintian, Yukang Li, Leilei Zhang, et al. "Biosynthetic Pathways and Functions of Indole-3-Acetic Acid in Microorganisms." Microorganisms 11, no. 8 (2023): 2077. http://dx.doi.org/10.3390/microorganisms11082077.
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Indole-3-acetic acid (IAA) belongs to the family of auxin indole derivatives. IAA regulates almost all aspects of plant growth and development, and is one of the most important plant hormones. In microorganisms too, IAA plays an important role in growth, development, and even plant interaction. Therefore, mechanism studies on the biosynthesis and functions of IAA in microorganisms can promote the production and utilization of IAA in agriculture. This mini-review mainly summarizes the biosynthesis pathways that have been reported in microorganisms, including the indole-3-acetamide pathway, indole-3-pyruvate pathway, tryptamine pathway, indole-3-acetonitrile pathway, tryptophan side chain oxidase pathway, and non-tryptophan dependent pathway. Some pathways interact with each other through common key genes to constitute a network of IAA biosynthesis. In addition, functional studies of IAA in microorganisms, divided into three categories, have also been summarized: the effects on microorganisms, the virulence on plants, and the beneficial impacts on plants.
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Muyzhnek, E. L., S. V. Nikulin, A. D. Kaprin, et al. "Antitumor Activity of Indole-3-carbinol in Breast Cancer Cells: Phenotype, Genetic Pattern, DNA Methylation Inversion." Biotekhnologiya 36, no. 2 (2020): 43–55. http://dx.doi.org/10.21519/0234-2758-2020-36-2-43-55.
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The effect of indole-3-carbinol on a number of functions and characteristics of MDA-MB-231 breast cancer cells and MCF-10A healthy breast tissue cells has been studied. It was shown that indole-3-carbinol significantly reduced the proliferation and migration of MDA-MB-231 cells and does not affect these functions in MCF-10A cells. Incubation of MDA-MB-231 tumor cells with indole-3-carbinol (100 uM) for 48 h resulted in a marked decrease in the expression of the Wnt cascade genes, CCND1 (by 28%), SP1 (by 44%), CDK6 (by 47%), as well as EGFR (by 64%) and FASN (by 22%) genes. Incubation of MCF-10A cell line under the same conditions induced a noticeable decrease in expression of only two genes, EGFR (by 16%) and CDK6 (by 9%). In addition, indole-3-carbinol was also shown to manifest a selective DNA demethylation activity in breast tumor cells and to reverse the process of abnormal methylation and functional blockage of the anti-tumor WIF1 gene. These data indicate that drags containing indole-3-carbinol as an active component can be potential regulators of epigenetic processes in the treatment of breast cancer and other tumors. indole-3-carbinol, breast cancer, epigenetics, Wnt
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Mayo, Juan C., and Rosa M. Sainz. "Melatonin from an Antioxidant to a Classic Hormone or a Tissue Factor: Experimental and Clinical Aspects 2019." International Journal of Molecular Sciences 21, no. 10 (2020): 3645. http://dx.doi.org/10.3390/ijms21103645.
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During the last 25 years we have accomplished great advances in melatonin research, regarding antioxidant or anti-inflammatory functions, oncostatic actions, glucose metabolism regulation or plant physiology, among others. Of course, we should not forget the classical, circadian-related functions of the indole, which has recently brought up new and important findings. All together these new discoveries will likely lead the way in the next decade in terms of melatonin research. This special issue collects some of these new advances focused on different aspects of the indole
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Lebrini, M., F. Robert, and C. Roos. "Adsorption Properties and Inhibition of C38 Steel Corrosion in Hydrochloric Solution by Some Indole Derivates: Temperature Effect, Activation Energies, and Thermodynamics of Adsorption." International Journal of Corrosion 2013 (2013): 1–13. http://dx.doi.org/10.1155/2013/139798.
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The corrosion rates in the presence of some indole derivates, namely, 9H-pyrido[3,4-b]indole (norharmane) and 1-methyl-9H-pyrido[3,4-b]indole (harmane), as inhibitors of C38 steel corrosion inhibitor in 1 M HCl solution, were measured by potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) techniques, in the range of temperatures from 25 to 55∘C. Results obtained revealed that the organic compounds investigated have inhibiting properties for all temperatures. The inhibition was assumed to occur via adsorption of the indole molecules on the metal surface. Adsorption of indole derivates was found to follow the Langmuir isotherm. The apparent activation energies, enthalpies, and entropies of the dissolution process and the free energies and enthalpies for the adsorption process were determined by potentiodynamic polarization and electrochemical impedance. The fundamental thermodynamic functions were used to collect important information about indole inhibitory behaviour.
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South, J. H. Exon, E. H. "DIETARY INDOLE-3-CARBINOL ALTERS IMMUNE FUNCTIONS IN RATS." Journal of Toxicology and Environmental Health, Part A 59, no. 4 (2000): 271–79. http://dx.doi.org/10.1080/009841000156934.
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Mueller, Carrie, Madhu Katepalli, Shelby Steinmeyer, Arul Jayaraman, and Robert Alaniz. "A role for microbiota metabolites in generation of mucosal dendritic cells (P3160)." Journal of Immunology 190, no. 1_Supplement (2013): 61.5. http://dx.doi.org/10.4049/jimmunol.190.supp.61.5.
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Abstract The gut mucosa normally exhibits tolerance towards the commensal microbiota by active suppression of inflammation. When homeostasis is disrupted, inflammatory bowel diseases may develop, during which microbiota dysbiosis may also occur. Resulting chronic inflammation induces loss of intestinal epithelial integrity, gastrointestinal (GI) distress, and colon cancer risk. We hypothesize that under normal conditions, the microbiota produce beneficial compounds that promote homeostasis. Previously, we reported that indole exerts immunomodulatory and anti-inflammatory effects on intestinal epithelial cells (IECs). We propose that indole, an abundant, freely diffusible, and strictly microbiota-derived molecule in the GI tract, conditions IECs and immune cells for optimal gut functions. Here, we report that indole potently modulates dendritic cell (DC) responses, which are central regulators of gut homeostasis. Specifically, indole-conditioned DCs produce decreased pro-inflammatory cytokines after microbial activation, and indole strongly synergizes with TGF-β for this effect. In addition, indole regulates the expression of the mucosal DC markers CCR9, B220, and aldh1a2. Furthermore, indole-treatment rescues host inflammation in a murine model of colitis. Given its availability and immunomodulatory properties, we suggest indole is a member of a novel class of microbiota compounds that regulate gut immune cells and may be a potential treatment of inflammatory bowel disease.
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Tsuchiya, Hironori. "Comparative Effects ofα-,β-, andγ-Carbolines on Platelet Aggregation and Lipid Membranes". Journal of Toxicology 2011 (2011): 1–9. http://dx.doi.org/10.1155/2011/151596.
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Cigarette smoking and alcohol consumption possibly affect platelet functions. To verify the hypothesis that someα-,β-, andγ-carboline components in cigarette smoke and alcoholic beverages may change platelet aggregability, their effects on human platelets were determined by aggregometry together with investigating their membrane effects by turbidimetry. Carbolines inhibited platelet aggregation induced by five agents with the potency being 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole > 3-amino-1-methyl-5H-pyrido[4,3-b]indole > 1-methyl-9H-pyrido[3,4-b]indole. The most potent 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole showed 50% aggregation-inhibitory concentrations of 6–172 μM. Bothγ-carbolines interacted with phosphatidylcholine membranes to lower the lipid phase transition temperature with the potency correlating to the antiplatelet activity, suggesting that the interaction with platelet membranes to increase their fluidity underlies antiplatelet effects. Given their possible concentration and accumulation in platelets,γ- andβ-carbolines would provide cigarette smokers and alcohol drinkers with reduced platelet aggregability, and they may be responsible for the occurrence of hemorrhagic diseases associated with heavy smoking and alcoholics.
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Pirog, T. P., D. V. Piatetska, N. O. Klymenko, and G. O. Iutynska. "Ways of Auxin Biosynthesis in Microorganisms." Mikrobiolohichnyi Zhurnal 84, no. 2 (2022): 57–72. http://dx.doi.org/10.15407/microbiolj84.02.057.
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Among plant hormones, auxins, in particular indole-3-acetic acid (IAA), are the most studied and researched. Almost all groups of soil microorganisms, both plant-associated and non-plant-associated bacteria, fungi, and phytopathogenic microorganisms are capable of producing auxins. The development of preparations for crop production is directly related to the production of bacterial strains with high auxin-synthesizing potential, which is possible only with a full understanding of the ways of regulation and synthesis of auxins in bacteria. The synthesis of auxins in microorganisms can take place in two ways: by the gradual conversion of tryptophan to IAA (tryptophan-dependent pathway) or by the use of other intermediates (tryptophan-independent pathway). The latter is poorly clarified, and in the literature available today, there is only a small amount of information on the functioning of this pathway in microorganisms. The review presents literature data on the ways of auxin biosynthesis in different groups of microorganisms, as well as approaches to the intensification of indole-3-acetic acid synthesis. The formation of IAA from tryptophan can be carried out in the following ways: through indole-3-pyruvate, through indole-3-acetamide, and through indole-3-acetonitrile. The vast majority of available publications are related to the assimilation of tryptophan through the formation of indole-3-pyruvate as this pathway is the most common among microorganisms. Thus, it functions in rhizospheric, symbiotic, endophytic, and free-living bacteria. The concentration of synthesized IAA among natural strains is in the range from 260 to 1130 μg/mL. Microorganisms in which the indole-3-acetamide pathway functions are characterized by lower auxin-synthesizing ability compared to those that assimilate tryptophan through indole-3-pyruvate. These include bacteria of the genera Streptomyces, Pseudomonas, and Bradyrhizobium and fungi of the genus Fusarium. The level of synthesis of IAA in such microorganisms is from 1.17×10−4 to 255.6 μg/mL. To date, only two strains that assimilate tryptophan via the indole-3-acetonitrile pathway and form up to 31.5 μg/mL IAA have been described in the available literature. To intensify the synthesis of indole-3-acetic acid, researchers use two main approaches: the first consists in introducing into the culture medium of exogenous precursors of biosynthesis (usually tryptophan, less often indole-3-pyruvate, indole-3-acetamide, and indole-3-acetonitrile); the second — in increasing the expression of the corresponding genes and creating recomindolebinant strains-supersynthetics of IAA. The largest number of publications is devoted to increasing the synthesis of IAA in the presence of biosynthesis precursors. Depending on the type of bacteria, the composition of the nutrient medium, and the amount of exogenously introduced precursor, the synthesis of the final product was increased by 1.2—27 times compared to that before the intensifi cation. Thus, in the presence of 11 g/L tryptophan, Enterobacter sp. DMKU-RP206 synthesized 5.56 g/L, while in a medium without the precursor, it yielded only 0.45 g/L IAA. Recombinant strains Corynebacterium glutamicum ATCC 13032 and Escherichia coli MG165 formed 7.1 and 7.3 g/L IAA, respectively, when tryptophan (10 g/L) was added to the culture medium. The level of auxin synthesis in microorganisms may be increased under stress conditions (temperature, pH, biotic and abiotic stress factors), but in this case, the IAA concentration does not exceed 100 mg/L, and therefore this method of intensification cannot compete with the others above.
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Gwon, Seon-Yeong, Sue-Yeon Lee, Young-A. Son, and Sung-Hoon Kim. "Benzothiazole and indole based dye sensor: Optical switching functions with pH stimuli." Fibers and Polymers 13, no. 9 (2012): 1101–4. http://dx.doi.org/10.1007/s12221-012-1101-0.
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Wu, Jun, Blair Moses Kamanga, Wenying Zhang, Yanhao Xu, and Le Xu. "Research progress of aldehyde oxidases in plants." PeerJ 10 (March 25, 2022): e13119. http://dx.doi.org/10.7717/peerj.13119.
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Plant aldehyde oxidases (AOs) are multi-functional enzymes, and they could oxidize abscisic aldehyde into ABA (abscisic acid) or indole acetaldehyde into IAA (indoleacetic acid) as the last step, respectively. AOs can be divided into four groups based on their biochemical and physiological functions. In this review, we summarized the recent studies about AOs in plants including the motif information, biochemical, and physiological functions. Besides their role in phytohormones biosynthesis and stress response, AOs could also involve in reactive oxygen species homeostasis, aldehyde detoxification and stress tolerance.
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Lee, Soon Goo, Kate Harline, Orchid Abar, et al. "The plant pathogen enzyme AldC is a long-chain aliphatic aldehyde dehydrogenase." Journal of Biological Chemistry 295, no. 40 (2020): 13914–26. http://dx.doi.org/10.1074/jbc.ra120.014747.
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Aldehyde dehydrogenases are versatile enzymes that serve a range of biochemical functions. Although traditionally considered metabolic housekeeping enzymes because of their ability to detoxify reactive aldehydes, like those generated from lipid peroxidation damage, the contributions of these enzymes to other biological processes are widespread. For example, the plant pathogen Pseudomonas syringae strain PtoDC3000 uses an indole-3-acetaldehyde dehydrogenase to synthesize the phytohormone indole-3-acetic acid to elude host responses. Here we investigate the biochemical function of AldC from PtoDC3000. Analysis of the substrate profile of AldC suggests that this enzyme functions as a long-chain aliphatic aldehyde dehydrogenase. The 2.5 Å resolution X-ray crystal of the AldC C291A mutant in a dead-end complex with octanal and NAD+ reveals an apolar binding site primed for aliphatic aldehyde substrate recognition. Functional characterization of site-directed mutants targeting the substrate- and NAD(H)-binding sites identifies key residues in the active site for ligand interactions, including those in the “aromatic box” that define the aldehyde-binding site. Overall, this study provides molecular insight for understanding the evolution of the prokaryotic aldehyde dehydrogenase superfamily and their diversity of function.
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Gilbert, Sarah, Alexander Poulev, William Chrisler, et al. "Auxin-Producing Bacteria from Duckweeds Have Different Colonization Patterns and Effects on Plant Morphology." Plants 11, no. 6 (2022): 721. http://dx.doi.org/10.3390/plants11060721.
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The role of auxin in plant–microbe interaction has primarily been studied using indole-3-acetic acid (IAA)-producing pathogenic or plant-growth-promoting bacteria. However, the IAA biosynthesis pathway in bacteria involves indole-related compounds (IRCs) and intermediates with less known functions. Here, we seek to understand changes in plant response to multiple plant-associated bacteria taxa and strains that differ in their ability to produce IRCs. We had previously studied 47 bacterial strains isolated from several duckweed species and determined that 79% of these strains produced IRCs in culture, such as IAA, indole lactic acid (ILA), and indole. Using Arabidopsis thaliana as our model plant with excellent genetic tools, we performed binary association assays on a subset of these strains to evaluate morphological responses in the plant host and the mode of bacterial colonization. Of the 21 tested strains, only four high-quantity IAA-producing Microbacterium strains caused an auxin root phenotype. Compared to the commonly used colorimetric Salkowski assay, auxin concentration determined by LC–MS was a superior indicator of a bacteria’s ability to cause an auxin root phenotype. Studies with the auxin response mutant axr1-3 provided further genetic support for the role of auxin signaling in mediating the root morphology response to IAA-producing bacteria strains. Interestingly, our microscopy results also revealed new evidence for the role of the conserved AXR1 gene in endophytic colonization of IAA-producing Azospirillum baldaniorum Sp245 via the guard cells.
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Walter, Antje, Lorenzo Caputi, Sarah O’Connor, Karl-Heinz van Pée, and Jutta Ludwig-Müller. "Chlorinated Auxins—How Does Arabidopsis Thaliana Deal with Them?" International Journal of Molecular Sciences 21, no. 7 (2020): 2567. http://dx.doi.org/10.3390/ijms21072567.
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Plant hormones have various functions in plants and play crucial roles in all developmental and differentiation stages. Auxins constitute one of the most important groups with the major representative indole-3-acetic acid (IAA). A halogenated derivate of IAA, 4-chloro-indole-3-acetic acid (4-Cl-IAA), has previously been identified in Pisum sativum and other legumes. While the enzymes responsible for the halogenation of compounds in bacteria and fungi are well studied, the metabolic pathways leading to the production of 4-Cl-IAA in plants, especially the halogenating reaction, are still unknown. Therefore, bacterial flavin-dependent tryptophan-halogenase genes were transformed into the model organism Arabidopsis thaliana. The type of chlorinated indole derivatives that could be expected was determined by incubating wild type A. thaliana with different Cl-tryptophan derivatives. We showed that, in addition to chlorinated IAA, chlorinated IAA conjugates were synthesized. Concomitantly, we found that an auxin conjugate synthetase (GH3.3 protein) from A. thaliana was able to convert chlorinated IAAs to amino acid conjugates in vitro. In addition, we showed that the production of halogenated tryptophan (Trp), indole-3-acetonitrile (IAN) and IAA is possible in transgenic A. thaliana in planta with the help of the bacterial halogenating enzymes. Furthermore, it was investigated if there is an effect (i) of exogenously applied Cl-IAA and Cl-Trp and (ii) of endogenously chlorinated substances on the growth phenotype of the plants.
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Buneeva, O. A., O. V. Gnedenko, M. V. Medvedeva, A. S. Ivanov, and A. E. Medvedev. "Oxidative modification of glyceraldehyde-3-phosphate dehydrogenase influences its interaction with endogenous neuroprotector isatin." Biomeditsinskaya Khimiya 62, no. 2 (2016): 160–63. http://dx.doi.org/10.18097/pbmc20166202160.
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Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a classical glycolytic redox sensitive enzyme, exhibits various non-glycolytic functions, which are considered to be especially important for progression of various neurodegenerative diseases. GAPDH binds isatin (indole-dione-2,3), an endogenous indole often used as a parent component in numerous derivatives demonstrating diverse pharmacological (including neuroprotector) activities. In this study we have investigated binding of intact and mildly oxidized GAPDH to immobilized isatin, using an optical biosensor technique, employing surface plasmon resonance (SPR), and the effect of isatin as a probe for this binding. Mild GAPDH oxidation by 70 mM H2O2 increased enzyme dissociation from immobilized isatin. Since GAPDH is considered as a putative target for various neuroprotector agents, this suggests that its redox state determines sensitivity to neuroprotective agents, and oxidative stress typical for various neurodegenerative disorders may significantly reduce pharmacological effectiveness of such compounds
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Cao, Xu, Honglei Yang, Chunqiong Shang, Sang Ma, Li Liu, and Jialing Cheng. "The Roles of Auxin Biosynthesis YUCCA Gene Family in Plants." International Journal of Molecular Sciences 20, no. 24 (2019): 6343. http://dx.doi.org/10.3390/ijms20246343.
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Auxin plays essential roles in plant normal growth and development. The auxin signaling pathway relies on the auxin gradient within tissues and cells, which is facilitated by both local auxin biosynthesis and polar auxin transport (PAT). The TRYPTOPHAN AMINOTRANSFERASE OF ARABIDOPSIS (TAA)/YUCCA (YUC) pathway is the most important and well-characterized pathway that plants deploy to produce auxin. YUCs function as flavin-containing monooxygenases (FMO) catalyzing the rate-limiting irreversible oxidative decarboxylation of indole-3-pyruvate acid (IPyA) to form indole-3-acetic acid (IAA). The spatiotemporal dynamic expression of different YUC gene members finely tunes the local auxin biosynthesis in plants, which contributes to plant development as well as environmental responses. In this review, the recent advances in the identification, evolution, molecular structures, and functions in plant development and stress response regarding the YUC gene family are addressed.
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Bakar-Ates, Filiz. "The Indole Phytoalexin Derivatives Induced a Significant Inhibition on Src Kinase Activity of Human Cancer Cells." Proceedings 22, no. 1 (2019): 3. http://dx.doi.org/10.3390/proceedings2019022003.
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The Src, a protein kinase, is a family of protein tyrosine kinases (SFKs), and this protein catalyses the phosphorylation of tyrosine. The studies have revealed its key roles in regulating signal transduction from cell surface receptors. The Src kinases act as cytoplasmic signalling machinery through regulating various cellular processes, such as cell growth, differentiation, migration, and survival. The pleiotropic functions of the Src family emphasise the importance of family members which have also been accepted as cellular oncogenes. Indole phytoalexins, which have been identified in various plants, have a structure with indole nucleus with the side chain or a heterocycle containing nitrogen and sulphur atoms. The antiproliferative effects of some phytoalexins have been demonstrated in various cancers. Among the members of phytoalexins, brassinin is known with a dithiocarbamate moiety and S-alkyl piece linked to indole core, and camalexin has an indole structure substituted at position 3 by the 1,3-thiazol-2-yl group. The inhibitory effects of these compounds on cancer cell proliferation have been reported. The aim of this study is to evaluate the effects of compounds on Src kinase activity. Human MCF-7 breast carcinoma and SW480 colorectal carcinoma cells were treated with compounds, and the effects of compounds on Src kinase activity were evaluated by Src-tyrosine kinase assay. The data were also compared with the growth inhibitory potential of compounds. The results have shown that both brassinin and camalexin have significantly inhibited the activity of Src kinase at 10 mM and higher concentrations in MCF-7 and SW480 cell lines (p < 0.05). In conclusion, this study is the first to evaluate the role of indole phytoalexins on the Src kinase activity of cancer cells. The data obtained have proven that the indole phytoalexin structure can show anticancer activity as Src mediated. It is thought that existing data will shed light on novel anticancer drug development studies.
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Crocetti, Letizia, Gabriella Guerrini, Maria Paola Giovannoni, et al. "New Panx-1 Blockers: Synthesis, Biological Evaluation and Molecular Dynamic Studies." International Journal of Molecular Sciences 23, no. 9 (2022): 4827. http://dx.doi.org/10.3390/ijms23094827.
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The channel protein Panx-1 is involved in some pathologies, such as epilepsy, ischemic stroke, cancer and Parkinson’s disease, as well as in neuropathic pain. These observations make Panx-1 an interesting biological target. We previously published some potent indole derivatives as Panx-1 blockers, and as continuation of the research in this field we report here the studies on additional chemical scaffolds, naphthalene and pyrazole, appropriately substituted with those functions that gave the best results as in our indole series (sulphonamide functions and one/two carboxylic groups) and in Panx-1 blockers reported in the literature (sulphonic acid). Compounds 4 and 13, the latter being an analogue of the drug Probenecid, are the most potent Panx-1 blockers obtained in this study, with I = 97% and I = 93.7% at 50 µM, respectively. Both compounds, tested in a mouse model of oxaliplatin-induced neuropathic pain, showed a similar anti-hypersensitivity profile and are able to significantly increase the mouse pain threshold 45 min after the injection of the doses of 1 nmol and 3 nmol. Finally, the molecular dynamic studies and the PCA analysis have made it possible to identify a discriminating factor able to separate active compounds from inactive ones.
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Negri, Stefano, Mauro Commisso, Linda Avesani, and Flavia Guzzo. "The case of tryptamine and serotonin in plants: a mysterious precursor for an illustrious metabolite." Journal of Experimental Botany 72, no. 15 (2021): 5336–55. http://dx.doi.org/10.1093/jxb/erab220.
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Abstract Indolamines are tryptophan-derived specialized metabolites belonging to the huge and ubiquitous indole alkaloids group. Serotonin and melatonin are the best-characterized members of this family, given their many hormonal and physiological roles in animals. Following their discovery in plants, the study of plant indolamines has flourished and their involvement in important processes, including stress responses, growth and development, and reproduction, has been proposed, leading to their classification as a new category of phytohormones. However, the complex indolamine puzzle is far from resolved, particularly the biological roles of tryptamine, the early serotonin precursor representing the central hub of many downstream indole alkaloids. Tryptophan decarboxylase, which catalyzes the synthesis of tryptamine, strictly regulates the flux of carbon and nitrogen from the tryptophan pool into the indolamine pathway. Furthermore, tryptamine accumulates to high levels in the reproductive organs of many plant species and therefore cannot be classed as a mere intermediate but rather as an end product with potentially important functions in fruits and seeds. This review summarizes current knowledge on the role of tryptamine and its close relative serotonin, emphasizing the need for a clear understanding of the functions of, and mutual relations between, these indolamines and their biosynthesis pathways in plants.
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Shcherbakova, E. S., T. S. Sall, S. I. Sitkin, T. Ya Vakhitov, and E. V. Demyanova. "The role of bacterial metabolites derived from aromatic amino acids in non-alcoholic fatty liver disease." Almanac of Clinical Medicine 48, no. 6 (2020): 375–86. http://dx.doi.org/10.18786/2072-0505-2020-48-066.
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The review deals with the role of aromatic amino acids and their microbial metabolites in the development and progression of non-alcoholic fatty liver disease (NAFLD). Pathological changes typical for NAFLD, as well as abnormal composition and/or functional activity of gut microbiota, results in abnormal aromatic amino acid metabolism. The authors discuss the potential of these amino acids and their bacterial metabolites to produce both negative and positive impact on the main steps of NAFLD pathophysiology, such as lipogenesis and inflammation, as well as on the liver functions through regulation of the intestinal barrier and microbiota-gut-liver axis signaling. The review gives detailed description of the mechanism of biological activity of tryptophan and its derivatives (indole, tryptamine, indole-lactic, indole-propyonic, indole-acetic acids, and indole-3-aldehyde) through the activation of aryl hydrocarbon receptor (AhR), preventing the development of liver steatosis. Bacteria-produced phenyl-alanine metabolites could promote liver steatosis (phenyl acetic and phenyl lactic acids) or, on the contrary, could reduce liver inflammation and increase insulin sensitivity (phenyl propionic acid). Tyramine, para-cumarate, 4-hydroxyphenylacetic acids, being by-products of bacterial catabolism of tyrosine, can prevent NAFLD, whereas para-cresol and phenol accelerate the progression of NAFLD by damaging the barrier properties of intestinal epithelium. Abnormalities in bacterial catabolism of tyrosine, leading to its excess, stimulate fatty acid synthesis and promote lipid infiltration of the liver. The authors emphasize a close interplay between bacterial metabolism of aromatic amino acids by gut microbiota and the functioning of the human body. They hypothesize that microbial metabolites of aromatic amino acids may represent not only therapeutic targets or non-invasive biomarkers, but also serve as bioactive agents for NAFLD treatment and prevention.
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Pfalz, Marina, Michael Dalgaard Mikkelsen, Paweł Bednarek, Carl Erik Olsen, Barbara Ann Halkier, and Juergen Kroymann. "Metabolic Engineering in Nicotiana benthamiana Reveals Key Enzyme Functions in Arabidopsis Indole Glucosinolate Modification." Plant Cell 23, no. 2 (2011): 716–29. http://dx.doi.org/10.1105/tpc.110.081711.
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Mano, Y., K. Nemoto, M. Suzuki, H. Seki, I. Fujii, and T. Muranaka. "The AMI1 gene family: indole-3-acetamide hydrolase functions in auxin biosynthesis in plants." Journal of Experimental Botany 61, no. 1 (2009): 25–32. http://dx.doi.org/10.1093/jxb/erp292.
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Gitis, Valeri, Alexander Derendyaev, Konstantin Petrov, et al. "Monotonic Functions Method and Its Application to Staging of Patients with Prostate Cancer According to Pretreatment Data." Applied Sciences 11, no. 9 (2021): 3836. http://dx.doi.org/10.3390/app11093836.
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Prostate cancer is the second most frequent malignancy (after lung cancer). Preoperative staging of PCa is the basis for the selection of adequate treatment tactics. In particular, an urgent problem is the classification of indolent and aggressive forms of PCa in patients with the initial stages of the tumor process. To solve this problem, we propose to use a new binary classification machine-learning method. The proposed method of monotonic functions uses a model in which the disease’s form is determined by the severity of the patient’s condition. It is assumed that the patient’s condition is the easier, the less the deviation of the indicators from the normal values inherent in healthy people. This assumption means that the severity (form) of the disease can be represented by monotonic functions from the values of the deviation of the patient’s indicators beyond the normal range. The method is used to solve the problem of classifying patients with indolent and aggressive forms of prostate cancer according to pretreatment data. The learning algorithm is nonparametric. At the same time, it allows an explanation of the classification results in the form of a logical function. To do this, you should indicate to the algorithm either the threshold value of the probability of successful classification of patients with an indolent form of PCa, or the threshold value of the probability of misclassification of patients with an aggressive form of PCa disease. The examples of logical rules given in the article show that they are quite simple and can be easily interpreted in terms of preoperative indicators of the form of the disease.
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Watanabe, Shunsuke, Naoki Takahashi, Yuri Kanno, et al. "TheArabidopsisNRT1/PTR FAMILY protein NPF7.3/NRT1.5 is an indole-3-butyric acid transporter involved in root gravitropism." Proceedings of the National Academy of Sciences 117, no. 49 (2020): 31500–31509. http://dx.doi.org/10.1073/pnas.2013305117.
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Active membrane transport of plant hormones and their related compounds is an essential process that determines the distribution of the compounds within plant tissues and, hence, regulates various physiological events. Here, we report that theArabidopsisNITRATE TRANSPORTER 1/PEPTIDE TRANSPORTER FAMILY 7.3 (NPF7.3) protein functions as a transporter of indole-3-butyric acid (IBA), a precursor of the major endogenous auxin indole-3-acetic acid (IAA). When expressed in yeast, NPF7.3 mediated cellular IBA uptake. Loss-of-functionnpf7.3mutants showed defective root gravitropism with reduced IBA levels and auxin responses. Nevertheless, the phenotype was restored by exogenous application of IAA but not by IBA treatment.NPF7.3was expressed in pericycle cells and the root tip region including root cap cells of primary roots where the IBA-to-IAA conversion occurs. Our findings indicate that NPF7.3-mediated IBA uptake into specific cells is required for the generation of appropriate auxin gradients within root tissues.
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Wang, Bing, Jinfang Chu, Tianying Yu, et al. "Tryptophan-independent auxin biosynthesis contributes to early embryogenesis in Arabidopsis." Proceedings of the National Academy of Sciences 112, no. 15 (2015): 4821–26. http://dx.doi.org/10.1073/pnas.1503998112.
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The phytohormone auxin regulates nearly all aspects of plant growth and development. Tremendous achievements have been made in elucidating the tryptophan (Trp)-dependent auxin biosynthetic pathway; however, the genetic evidence, key components, and functions of the Trp-independent pathway remain elusive. Here we report that the Arabidopsis indole synthase mutant is defective in the long-anticipated Trp-independent auxin biosynthetic pathway and that auxin synthesized through this spatially and temporally regulated pathway contributes significantly to the establishment of the apical–basal axis, which profoundly affects the early embryogenesis in Arabidopsis. These discoveries pave an avenue for elucidating the Trp-independent auxin biosynthetic pathway and its functions in regulating plant growth and development.
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Reiter, Russel J., Dun Xian Tan, and Annia Galano. "Melatonin: Exceeding Expectations." Physiology 29, no. 5 (2014): 325–33. http://dx.doi.org/10.1152/physiol.00011.2014.
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Melatonin is a small, highly conserved indole with numerous receptor-mediated and receptor-independent actions. Receptor-dependent functions include circadian rhythm regulation, sleep, and cancer inhibition. The receptor-independent actions relate to melatonin's ability to function in the detoxification of free radicals, thereby protecting critical molecules from the destructive effects of oxidative stress under conditions of ischemia/reperfusion injury (stroke, heart attack), ionizing radiation, and drug toxicity, among others. Melatonin has numerous applications in physiology and medicine.
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Prudhomme, Michelle. "lndolocarbazoles as Anti-Cancer Agents." Current Pharmaceutical Design 3, no. 3 (1997): 265–90. http://dx.doi.org/10.2174/138161280303221007123245.
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Abstract: Protein kinase C (PKC) is a family of phospholipid-dependent serine/threonine protein kinases that plays a key role in signal transduction. Consequently, PKC controls a large variety of cellular processes such as proliferation and differentiation as well as smooth muscle contraction and secretions. The disruption of these processes would have severe implications for many physiological functions. The twelve known PKC isoenzymes show great variations in their substrate specificity and their distribution among different tissues, indicating their specialised role in certain tissue functions. Altered expression of PKC isoenzymes has been reported in a wide range of diseases. DNA topoisomerase I is a nuclear enzyme, involved in replication, transcription and recombination, that modifies and regulates the topological state of DNA. Many microbial metabolites and synthetic compounds possessing an indolocarbazole unit are biologically active products with antitumor properties. Antibiotic indolocarbazoles staurosporine, K-252a, UCN-01 and 02 are known protein kinase C inhibitors while structurally related rebeccamycin and ED-110 are topoisomerase I inhibitors without inhibitory effect against PKC. This review will update efforts made toward the discovery of antitumor indolocarbazoles and their possible mode of action via either PKC or topoisomerase I inhibition. Structure-activity relationship studies in a series of maleamide and maleimide indolocarbazoles bearing or not a sugar moiety linked either to both indole nitrogens such as staurosporine, or to one indole nitrogen such as rebeccamycin, will be reported.
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Kliebenstein, Daniel J., Jonathan Gershenzon, and Thomas Mitchell-Olds. "Comparative Quantitative Trait Loci Mapping of Aliphatic, Indolic and Benzylic Glucosinolate Production in Arabidopsis thaliana Leaves and Seeds." Genetics 159, no. 1 (2001): 359–70. http://dx.doi.org/10.1093/genetics/159.1.359.
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Abstract Secondary metabolites are a diverse set of plant compounds believed to have numerous functions in plant-environment interactions. Despite this importance, little is known about the regulation of secondary metabolite accumulation. We are studying the regulation of glucosinolates, a large group of secondary metabolites, in Arabidopsis to investigate how secondary metabolism is controlled. We utilized Ler and Cvi, two ecotypes of Arabidopsis that have striking differences in both the types and amounts of glucosinolates that accumulate in the seeds and leaves. QTL analysis identified six loci determining total aliphatic glucosinolate accumulation, six loci controlling total indolic glucosinolate concentration, and three loci regulating benzylic glucosinolate levels. Our results show that two of the loci controlling total aliphatic glucosinolates map to biosynthetic loci that interact epistatically to regulate aliphatic glucosinolate accumulation. In addition to the six loci regulating total indolic glucosinolate concentration, mapping of QTL for the individual indolic glucosinolates identified five additional loci that were specific to subsets of the indolic glucosinolates. These data show that there are a large number of variable loci controlling glucosinolate accumulation in Arabidopsis thaliana.
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Lin, Hailing, Hongqiang Qiu, Yu Cheng, et al. "Gelsemium elegans Benth: Chemical Components, Pharmacological Effects, and Toxicity Mechanisms." Molecules 26, no. 23 (2021): 7145. http://dx.doi.org/10.3390/molecules26237145.
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Gelsemium elegans Benth (GEB), also known as heartbreak grass, is a highly poisonous plant belonging to the family Loganiaceae and genus Gelsemium that has broad application prospects in medicine. This article reviews its chemical components, pharmacological effects, toxicity mechanisms, and research progress in clinical applications in recent years. Indole alkaloids are the main active components of GEB and have a variety of pharmacological and biological functions. They have anti-tumor, anti-inflammatory, analgesic, and immunomodulation properties, with the therapeutic dose being close to the toxic dose. Application of small-dose indole alkaloids fails to work effectively, while high-dose usage is prone to poisoning, aggravating the patient’s conditions. Special caution is needed, especially to observe the changes in the disease condition of the patients in clinical practice. In-depth research on the chemical components and mechanisms of GEB is essential to the development of promising lead compounds and lays the foundation for extensive clinical application and safe usage of GEB in the future.
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Lőrinczi, Bálint, Péter Simon, and István Szatmári. "Synthesis of Indole-Coupled KYNA Derivatives via C–N Bond Cleavage of Mannich Bases." International Journal of Molecular Sciences 23, no. 13 (2022): 7152. http://dx.doi.org/10.3390/ijms23137152.
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KYNAs, a compound with endogenous neuroprotective functions and an indole that is a building block of many biologically active compounds, such as a variety of neurotransmitters, are reacted in a transformation building upon Mannich bases. The reaction yields triarylmethane derivatives containing two biologically potent skeletons, and it may contribute to the synthesis of new, specialised neuroprotective compounds. The synthesis has been investigated via two procedures and the results were compared to those of previous studies. A possible alternative reaction route through acid catalysis has been established.
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Qin, Miaomiao, Jing Wang, Tianyi Zhang, et al. "Genome-Wide Identification and Analysis on YUCCA Gene Family in Isatis indigotica Fort. and IiYUCCA6-1 Functional Exploration." International Journal of Molecular Sciences 21, no. 6 (2020): 2188. http://dx.doi.org/10.3390/ijms21062188.
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Auxin is one of the most critical hormones in plants. YUCCA (Tryptophan aminotransferase of Arabidopsis (TAA)/YUCCA) enzymes catalyze the key rate-limiting step of the tryptophan-dependent auxin biosynthesis pathway, from IPA (Indole-3-pyruvateacid) to IAA (Indole-3-acetic acid). Here, 13 YUCCA family genes were identified from Isatis indigotica, which were divided into four categories, distributing randomly on chromosomes (2n = 14). The typical and conservative motifs, including the flavin adenine dinucleotide (FAD)-binding motif and flavin-containing monooxygenases (FMO)-identifying sequence, existed in the gene structures. IiYUCCA genes were expressed differently in different organs (roots, stems, leaves, buds, flowers, and siliques) and developmental periods (7, 21, 60, and 150 days after germination). Taking IiYUCCA6-1 as an example, the YUCCA genes functions were discussed. The results showed that IiYUCCA6-1 was sensitive to PEG (polyethylene glycol), cold, wounding, and NaCl treatments. The over-expressed tobacco plants exhibited high auxin performances, and some early auxin response genes (NbIAA8, NbIAA16, NbGH3.1, and NbGH3.6) were upregulated with increased IAA content. In the dark, the contents of total chlorophyll and hydrogen peroxide in the transgenic lines were significantly lower than in the control group, with NbSAG12 downregulated and some delayed leaf senescence characteristics, which delayed the senescence process to a certain extent. The findings provide comprehensive insight into the phylogenetic relationships, chromosomal distributions, and expression patterns and functions of the YUCCA gene family in I. indigotica.
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Zhou, Cai-Jie, Bai-Ling Xie, Hai-Yang Han, et al. "Short-Chain Fatty Acids Promote Immunotherapy by Modulating Immune Regulatory Property in B Cells." Journal of Immunology Research 2021 (December 10, 2021): 1–13. http://dx.doi.org/10.1155/2021/2684361.
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The dysfunction of regulatory B cells (Breg) may result in immune inflammation such as allergic rhinitis (AR); the underlying mechanism is not fully understood yet. Short-chain fatty acids, such as propionic acid (PA), have immune regulatory functions. This study is aimed at testing a hypothesis that modulates PA production alleviating airway allergy through maintaining Breg functions. B cells were isolated from the blood obtained from AR patients and healthy control (HC) subjects. The stabilization of IL-10 mRNA in B cells was tested with RT-qPCR. An AR mouse model was developed to test the role of PA in stabilizing the IL-10 expression in B cells. We found that the serum PA levels were negatively correlated with the serum Th2 cytokine levels in AR patients. Serum PA levels were positively associated with peripheral CD5+ B cell frequency in AR patients; the CD5+ B cells were also IL-10+. The spontaneous IL-10 mRNA decay was observed in B cells, which was prevented by the presence of PA through activating GPR43. PA counteracted the effects of Tristetraprolin (TTP) on inducing IL-10 mRNA decay in B cells through the AKT/T-bet/granzyme B pathway. Administration of Yupinfeng San, a Chinese traditional medical formula, or indole-3-PA, induced PA production by intestinal bacteria to stabilize the IL-10 expression in B cells, which promoted the allergen specific immunotherapy, and efficiently alleviated experimental AR. In summary, the data show that CD5+ B cells produce IL-10. The serum lower PA levels are associated with the lower frequency of CD5+ B cells in AR patients. Administration with Yupinfeng San or indole-3-PA can improve Breg functions and alleviate experimental AR.
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Garty, Ben-Zion, Balu H. Athreya, Robert Wilmott, Nina Scarpa, Robert Doughty, and Steven D. Douglas. "Pulmonary Functions in Children With Progressive Systemic Sclerosis." Pediatrics 88, no. 6 (1991): 1161–67. http://dx.doi.org/10.1542/peds.88.6.1161.
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The patterns of pulmonary involvement in 13 children with progressive systemic sclerosis were investigated. Eight patients (61%) had respiratory symptoms or signs and 7 patients (55%) had abnormalities on chest roentgenogram. Twelve patients (92%) had abnormal pulmonary function tests: 7 had restrictive disease, 2 had obstructive disease, 2 had small airway disease, and 1 had an isolated reduction in the diffusing capacity of carbon monoxide. Nine patients had the test performed during the first year of illness, 3 during the second year, and 1 at 5 years. All patients had abnormal pulmonary function tests when first studied. Subsequent pulmonary function tests over a period of 3 to 10 years (mean 6.2 years) showed substantial changes in only 2 patients (1 patient had initial worsening of diffusing capacity of carbon monoxide followed by normalization and another patient showed improvement of obstructive disease). Two patients died during follow-up, 1 of pulmonary hypertension, the other of severe restrictive lung disease and myocardial fibrosis. The major findings of this study were (1) high frequency of pulmonary disease in children with progressive systemic sclerosis, (2) early involvement of the lungs, (3) relatively indolent progression of lung disease, and (4) the prognostic importance of the severity of pulmonary disease. Pulmonary manifestations of progressive systemic sclerosis in children appear to be similar to those of affected adults.
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Stepanova, Anna N., Jeonga Yun, Linda M. Robles, et al. "The Arabidopsis YUCCA1 Flavin Monooxygenase Functions in the Indole-3-Pyruvic Acid Branch of Auxin Biosynthesis." Plant Cell 23, no. 11 (2011): 3961–73. http://dx.doi.org/10.1105/tpc.111.088047.
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Xia, Yan, Xiliang Zheng, Erkang Wang, Dongfeng Li, Ruibin Hou, and Jin Wang. "Synthesis of adenosine analogues with indole moiety as human adenosine A 3 receptor ligands." Royal Society Open Science 5, no. 2 (2018): 171596. http://dx.doi.org/10.1098/rsos.171596.
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Adenosine is an endogenous modulator exerting its functions through the activation of four adenosine receptor (AR) subtypes, termed A 1 , A 2A , A 2B and A 3 , which belong to the G-protein-coupled receptor superfamily. The human A 3 AR (hA 3 AR) subtype is implicated in several cytoprotective functions. Therefore, hA 3 AR modulators, and in particular agonists, are sought for their potential application as anti-inflammatory, anti-cancer and cardioprotective agents. Here, we prepared novel adenosine derivatives with indole moiety as hA 3 AR ligands. According to the biological assay, we found that 2-substituents 11 were critical structural determinants for A 3 AR ligands ( K i = 111 nM). The observed structure–affinity relationships of this class of ligands were also exhaustively rationalized using the molecular modelling approach. This allows the investigation on the binding mode of the potential compound in the ligand-binding pocket of the human A 3 receptor. The results demonstrated that 11 can interact with the ASN250, GLN167, PHE168 and VAL178 through hydrogen bonding, which are shown to be important for ligand–receptor interaction.
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Kollath-Leiß, K., C. Bönniger, P. Sardar, and F. Kempken. "BEM46 Shows Eisosomal Localization and Association with Tryptophan-Derived Auxin Pathway in Neurospora crassa." Eukaryotic Cell 13, no. 8 (2014): 1051–63. http://dx.doi.org/10.1128/ec.00061-14.
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ABSTRACTBEM46 proteins are evolutionarily conserved, but their functions remain elusive. We reported previously that the BEM46 protein inNeurospora crassais targeted to the endoplasmic reticulum (ER) and is essential for ascospore germination. In the present study, we established abem46knockout strain ofN. crassa. This Δbem46mutant exhibited a level of ascospore germination lower than that of the wild type but much higher than those of the previously characterizedbem46-overexpressing and RNA interference (RNAi) lines. Reinvestigation of the RNAi transformants revealed two types of alternatively splicedbem46mRNA; expression of either type led to a loss of ascospore germination. Our results indicated that the phenotype was not due tobem46mRNA downregulation or loss but was caused by the alternatively spliced mRNAs and the peptides they encoded. Using theN. crassaortholog of the eisosomal protein PILA fromAspergillus nidulans, we further demonstrated the colocalization of BEM46 with eisosomes. Employing the yeast two-hybrid system, we identified a single interaction partner: anthranilate synthase component II (encoded bytrp-1). This interaction was confirmedin vivoby a split-YFP (yellow fluorescent protein) approach. The Δtrp-1mutant showed reduced ascospore germination and increased indole production, and we used bioinformatic tools to identify a putative auxin biosynthetic pathway. The genes involved exhibited various levels of transcriptional regulation in the differentbem46transformant and mutant strains. We also investigated the indole production of the strains in different developmental stages. Our findings suggested that the regulation of indole biosynthesis genes was influenced bybem46overexpression. Furthermore, we uncovered evidence of colocalization of BEM46 with the neutral amino acid transporter MTR.
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Otten, Léon, and Anne Helfer. "Biological Activity of the rolB-like 5′ End of the A4-orf8 Gene from the Agrobacterium rhizogenes TL-DNA." Molecular Plant-Microbe Interactions® 14, no. 3 (2001): 405–11. http://dx.doi.org/10.1094/mpmi.2001.14.3.405.
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The iaaM gene from different plant-associated bacteria encodes a tryptophan monooxygenase (IaaM) that catalyzes the synthesis of indole-3-acetamide (IAM), a precursor of indole-3-acetic acid (IAA). Unlike the IaaM proteins from other bacteria, Agrobacterium spp. T-DNA-encoded IaaM proteins carry a 200 amino acid N-terminal extension with low homology to various members of the RolB protein family. This family is composed of 18 highly divergent T-DNA-encoded proteins, the basic functions of which are still largely undetermined. Deletion of the 5′rolB-like extension of the iaaM gene from Agrobacterium tumefaciens strain Ach5 did not lead to a reduction in IAM synthesis in plants. When expressed in tobacco, the rolB-like fragment did not affect growth or morphology. An iaaM homolog (A4-orf8) from the TL-DNA of Agrobacterium rhizogenes strain A4 also was investigated. Neither the full-size A4-orf8 gene nor the 5′-truncated form induced detectable IAM synthesis. Plants expressing the rolB-like part of the A4-orf8 gene, however, were dwarfed and mottled to various extents and synthesized abnormally high amounts of glucose, fructose, sucrose, and starch.
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Dixon, David P., Jonathan D. Sellars, and Robert Edwards. "The Arabidopsis phi class glutathione transferase AtGSTF2: binding and regulation by biologically active heterocyclic ligands." Biochemical Journal 438, no. 1 (2011): 63–70. http://dx.doi.org/10.1042/bj20101884.
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The plant-specific phi class of glutathione transferases (GSTFs) are often highly stress-inducible and expressed in a tissue-specific manner, suggestive of them having important protective roles. To date, these functions remain largely unknown, although activities associated with the binding and transport of reactive metabolites have been proposed. Using a sensitive and selective binding screen, we have probed the Arabidopsis thaliana GSTFs for natural product ligands from bacteria and plants. Uniquely, when overexpressed in bacteria, family members GSTF2 and GSTF3 bound a series of heterocyclic compounds, including lumichrome, harmane, norharmane and indole-3-aldehyde. When screened against total metabolite extracts from A. thaliana, GSTF2 also selectively bound the indole-derived phytoalexin camalexin, as well as the flavonol quercetin-3-O-rhamnoside. In each case, isothermal titration calorimetry revealed high-affinity binding (typically Kd<1 μM), which was enhanced in the presence of glutathione and by the other heterocyclic ligands. With GSTF2, these secondary ligand associations resulted in an allosteric enhancement in glutathione-conjugating activity. Together with the known stress responsiveness of GSTF2 and its association with membrane vesicles, these results are suggestive of roles in regulating the binding and transport of defence-related compounds in planta.
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Nemoto, Keiichirou, Masamitsu Hara, Masashi Suzuki, Hikaru Seki, Toshiya Muranaka, and Yoshihiro Mano. "TheNtAMI1gene functions in cell division of tobacco BY-2 cells in the presence of indole-3-acetamide." FEBS Letters 583, no. 2 (2008): 487–92. http://dx.doi.org/10.1016/j.febslet.2008.12.049.
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