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Articoli di riviste sul tema "Pharmacomodulations"

Autore: Grafiati

Pubblicato: 25 gennaio 2025

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1

Marc, Sylvain, Christophe Mésangeau, Mathilde Coevoet, Amélie Barczyk, Stéphane Burlet, Philippe Verwaerde, Cecilia Estrella et al. "Pharmacomodulations around an anti-Alzheimer drug-candidate". European Journal of Medicinal Chemistry Reports 4 (aprile 2022): 100020. http://dx.doi.org/10.1016/j.ejmcr.2021.100020.

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Logé, Cédric, Valérie Wallez, Elizabeth Scalbert, Christelle Cario-Tourmaniantz, Gervaise Loirand, Pierre Pacaud e Daniel Lesieur. "Rho-kinase Inhibitors: Pharmacomodulations on the Lead Compound Y-32885". Journal of Enzyme Inhibition and Medicinal Chemistry 17, n. 6 (1 gennaio 2002): 381–90. http://dx.doi.org/10.1080/1475636021000005659.

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3

Messire, Gatien, Patrick Rollin, Isabelle Gillaizeau e Sabine Berteina-Raboin. "Synthetic Modifications of Andrographolide Targeting New Potential Anticancer Drug Candidates: A Comprehensive Overview". Molecules 29, n. 12 (18 giugno 2024): 2884. http://dx.doi.org/10.3390/molecules29122884.

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This review collects the synthetic modifications performed on andrographolide, a natural molecule derived from Andrographis paniculata, for oncology applications. Various pharmacomodulations were carried out, and the products were tested on different cancer cell lines. The impact of these modifications was analyzed with the aim of mapping the positions essential for activity to facilitate future research in this field. However, this study makes it clear that, in addition to structural modifications of the molecule, which can result in varying degrees of effectiveness in targeting interactions, the lipophilic capacity of the structures obtained through hemisynthesis is of significant importance.

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Logé, Cédric, Xavier Siomboing, Valérie Wallez, Elizabeth Scalbert, Caroline Bennejean, Christelle Cario-Tourmaniantz, Gervaise Loirand, Bernard Gressier, Pierre Pacaud e Michel Luyckx. "Synthesis and Pharmacological Study of Rho-Kinase Inhibitors: Pharmacomodulations on the Lead Compound Fasudil". Journal of Enzyme Inhibition and Medicinal Chemistry 18, n. 2 (1 aprile 2003): 127–38. http://dx.doi.org/10.1080/1475636031000093561.

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5

Ameryckx, Alice, Lionel Pochet, Gang Wang, Esra Yildiz, Bouazza Es Saadi, Johan Wouters, Françoise Van Bambeke e Raphaël Frédérick. "Pharmacomodulations of the benzoyl-thiosemicarbazide scaffold reveal antimicrobial agents targeting d-alanyl-d-alanine ligase in bacterio". European Journal of Medicinal Chemistry 200 (agosto 2020): 112444. http://dx.doi.org/10.1016/j.ejmech.2020.112444.

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6

Stern, Eric, Giulio G. Muccioli, Barbara Bosier, Laurie Hamtiaux, Régis Millet, Jacques H. Poupaert, Jean-Pierre Hénichart, Patrick Depreux, Jean-François Goossens e Didier M. Lambert. "Pharmacomodulations around the 4-Oxo-1,4-dihydroquinoline-3-carboxamides, a Class of Potent CB2-Selective Cannabinoid Receptor Ligands: Consequences in Receptor Affinity and Functionality". Journal of Medicinal Chemistry 50, n. 22 (novembre 2007): 5471–84. http://dx.doi.org/10.1021/jm070387h.

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7

Mustière, Romain, Prisca Lagardère, Sébastien Hutter, Céline Deraeve, Florian Schwalen, Dyhia Amrane, Nicolas Masurier et al. "Pd-catalyzed C–C and C–N cross-coupling reactions in 2-aminothieno[3,2-d]pyrimidin-4(3H)-one series for antiplasmodial pharmacomodulation". RSC Advances 12, n. 31 (2022): 20004–21. http://dx.doi.org/10.1039/d2ra01687g.

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Pharmacomodulation at position 6 of a thienopyrimidinone antiplasmodial hit using palladium-catalyzed cross-coupling reactions afforded 33 new compounds, among which a new hit was found with enhanced metabolic stability.

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8

Mouysset, Geneviève, Marc Payard, Gérard Grassy, Pierre Tronche, Hubert Dabire, Paule Mouille e Henri Schmitt. "Pharmacomodulation d'adrénolytiques aα en série benzopyrannique". European Journal of Medicinal Chemistry 22, n. 6 (novembre 1987): 539–44. http://dx.doi.org/10.1016/0223-5234(87)90294-7.

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9

Varache-Béranger, Martine, Alain Nuhrich e Guy Devaux. "Pharmacomodulation d'arylcétones thiophéniques anti-agrégantes plaquettaires". European Journal of Medicinal Chemistry 23, n. 6 (novembre 1988): 501–10. http://dx.doi.org/10.1016/0223-5234(88)90092-x.

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10

Renault, Jacques, Aurelie Bernard, Solenn Brajeul, Pierre Verhaeghe, Sabrina Butt, Frederic Fabis, François Dauphin, Philippe Uriac e Sylvain Rault. "Pharmacomodulation of a Sulfamide 5-HT6 Receptor Ligand". Journal of Enzyme Inhibition and Medicinal Chemistry 19, n. 6 (1 dicembre 2004): 577–83. http://dx.doi.org/10.1080/14756360400004540.

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11

Lokich, Jacob. "Improving 5-Fluorouracil: Biomodulation, Pharmacomodulation, or Infusional Administration Schedules?" Cancer Investigation 16, n. 4 (gennaio 1998): 293–94. http://dx.doi.org/10.3109/07357909809039780.

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12

Kieffer, Charline, Anita Cohen, Pierre Verhaeghe, Lucie Paloque, Sébastien Hutter, Caroline Castera-Ducros, Michèle Laget et al. "Antileishmanial pharmacomodulation in 8-nitroquinolin-2(1H)-one series". Bioorganic & Medicinal Chemistry 23, n. 10 (maggio 2015): 2377–86. http://dx.doi.org/10.1016/j.bmc.2015.03.064.

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13

Bloss, Cynthia S. "Pharmacomodulation of the Gut: Implications for the Enterally Fed Patient". Nutrition in Clinical Practice 13, n. 5 (ottobre 1998): 201–14. http://dx.doi.org/10.1177/088453369801300502.

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14

Simion, Viorel, Wissem Nadim, Helene Benedetti, Chantal Pichon, Severine Morisset-Lopez e Patrick Baril. "Pharmacomodulation of microRNA Expression in Neurocognitive Diseases: Obstacles and Future Opportunities". Current Neuropharmacology 15, n. 2 (4 gennaio 2017): 276–90. http://dx.doi.org/10.2174/1570159x14666160630210422.

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15

Holloway, Richard H. "Systemic pharmacomodulation of transient lower esophageal sphincter relaxations11Reprints are not available." American Journal of Medicine 111, n. 8 (dicembre 2001): 178–85. http://dx.doi.org/10.1016/s0002-9343(01)00853-1.

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16

Vu, Thi Huyen, Erika Adhel, Katarina Vielfort, Ngûyet-Thanh Ha Duong, Guillaume Anquetin, Katy Jeannot, Philippe Verbeke, Sofia Hjalmar, Åsa Gylfe e Nawal Serradji. "Modified Fluoroquinolones as Antimicrobial Compounds Targeting Chlamydia trachomatis". International Journal of Molecular Sciences 23, n. 12 (16 giugno 2022): 6741. http://dx.doi.org/10.3390/ijms23126741.

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Abstract (sommario):

Chlamydia trachomatis causes the most common sexually transmitted bacterial infection and trachoma, an eye infection. Untreated infections can lead to sequelae, such as infertility and ectopic pregnancy in women and blindness. We previously enhanced the antichlamydial activity of the fluoroquinolone ciprofloxacin by grafting a metal chelating moiety onto it. In the present study, we pursued this pharmacomodulation and obtained nanomolar active molecules (EC50) against this pathogen. This gain in activity prompted us to evaluate the antibacterial activity of this family of molecules against other pathogenic bacteria, such as Neisseria gonorrhoeae and bacteria from the ESKAPE group. The results show that the novel molecules have selectively improved activity against C. trachomatis and demonstrate how the antichlamydial effect of fluoroquinolones can be enhanced.

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17

Milano, G., J.-M. Ferrero e E. François. "Comparative pharmacology of oral fluoropyrimidines: a focus on pharmacokinetics, pharmacodynamics and pharmacomodulation". British Journal of Cancer 91, n. 4 (27 luglio 2004): 613–17. http://dx.doi.org/10.1038/sj.bjc.6601973.

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18

Port, M., C. Corot, O. Rousseaux, I. Raynal e P. Bourrinet. "CMR 2005: 13.04: Design and pharmacomodulation of high-relaxivity MR contrast agents". Contrast Media & Molecular Imaging 1, n. 2 (2006): 87–88. http://dx.doi.org/10.1002/cmmi.76.

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19

Stefflova, Klara, Hui Li, Juan Chen e Gang Zheng. "Peptide-Based Pharmacomodulation of a Cancer-Targeted Optical Imaging and Photodynamic Therapy Agent". Bioconjugate Chemistry 18, n. 2 (marzo 2007): 379–88. http://dx.doi.org/10.1021/bc0602578.

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20

Toth, Peter P. "Pharmacomodulation of High-Density Lipoprotein Metabolism as a Therapeutic Intervention for Atherosclerotic Disease". Current Cardiology Reports 12, n. 6 (26 agosto 2010): 481–87. http://dx.doi.org/10.1007/s11886-010-0136-3.

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21

Zhang, Chen, Marie-Lise Maddelein, Raymond Wai-Yin Sun, Heinz Gornitzka, Olivier Cuvillier e Catherine Hemmert. "Pharmacomodulation on Gold-NHC complexes for anticancer applications – is lipophilicity the key point?" European Journal of Medicinal Chemistry 157 (settembre 2018): 320–32. http://dx.doi.org/10.1016/j.ejmech.2018.07.070.

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22

Chhour, Monivan, Agnès Aubouy, Sandra Bourgeade-Delmas, Pierre Pério, Hélène Ternet-Fontebasso, Mahamane Haidara, Gilles Ferry, Françoise Nepveu, Jean A. Boutin e Karine Reybier. "Antimalarial Properties of Dunnione Derivatives as NQO2 Substrates". Molecules 24, n. 20 (15 ottobre 2019): 3697. http://dx.doi.org/10.3390/molecules24203697.

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Dunnione, a natural product isolated from the leaves of Streptocarpus dunnii (Gesneriaceae), acts as a substrate for quinone-reductases that may be associated with its antimalarial properties. Following our exploration of reactive oxygen species-producing compounds such as indolones, as possible new approaches for the research of new ways to treat this parasitosis, we explored derivatives of this natural product and their possible antiplasmodial and antimalarial properties, in vitro and in vivo, respectively. Apart from one compound, all the products tested had weak to moderate antiplasmodial activities, the best IC50 value being equal to 0.58 µM. In vivo activities in the murine model were moderate (at a dose of 50 mg/kg/mice, five times higher than the dose of chloroquine). These results encourage further pharmacomodulation steps to improve the targeting of the parasitized red blood cells and antimalarial activities.

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Ilić, Budimir S., Dragoljub L. Miladinović, Branislava D. Kocić, Boban R. Spalović, Marija S. Marković, Hristina Čolović e Dejan M. Nikolić. "Chemoinformatic Investigation of Antibiotic Antagonism: The Interference of Thymus glabrescens Essential Oil Components with the Action of Streptomycin". Natural Product Communications 12, n. 10 (ottobre 2017): 1934578X1701201. http://dx.doi.org/10.1177/1934578x1701201033.

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Given the importance of Thymus glabrescens as a useful antibacterial remedy, we have evaluated the antibacterial and streptomycin-modifying activity of Thymus glabrescens essential oil, geraniol, geranyl acetate and thymol. It was shown that all substance-streptomycin combinations produced predominantly antagonistic interactions. Furthermore, combinations between geraniol and thymol showed dominant additive effect. Chemoinformatics results, combined with experimental data, suggest that antagonistic interactions with streptomycin were not a consequence of the antimicrobial action at the same target, but an outcome of the membrane impairment, followed by the membrane potential/proton motive force dissipation, which decreased the streptomycin uptake. Furthermore, the membrane toxicity of geraniol and thymol was confirmed by their additive antibacterial interactions and parameters of their penetration and accumulation throughout a cell membrane. This study should greatly help in an intelligent and a controlled pharmacomodulation of antibiotics.

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24

Yang, Felix, Andy Sivils, Victoria Cegielski, Som Singh e Xiang-Ping Chu. "Transient Receptor Potential (TRP) Channels in Pain, Neuropsychiatric Disorders, and Epilepsy". International Journal of Molecular Sciences 24, n. 5 (1 marzo 2023): 4714. http://dx.doi.org/10.3390/ijms24054714.

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Pharmacomodulation of membrane channels is an essential topic in the study of physiological conditions and disease status. Transient receptor potential (TRP) channels are one such family of nonselective cation channels that have an important influence. In mammals, TRP channels consist of seven subfamilies with a total of twenty-eight members. Evidence shows that TRP channels mediate cation transduction in neuronal signaling, but the full implication and potential therapeutic applications of this are not entirely clear. In this review, we aim to highlight several TRP channels which have been shown to mediate pain sensation, neuropsychiatric disorders, and epilepsy. Recent findings suggest that TRPM (melastatin), TRPV (vanilloid), and TRPC (canonical) are of particular relevance to these phenomena. The research reviewed in this paper validates these TRP channels as potential targets of future clinical treatment and offers patients hope for more effective care.

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25

Al Saadi, Noor Thamer Abbas, Marwah Thamer Abbas Al Saadi e Zina Tahsin Ali. "Pharmacomodulation of positions two & four of nucleus five-nitroimidazole by using palladium catalyze". Annals of Tropical Medicine and Public Health 22, n. 07 (2019): 08–18. http://dx.doi.org/10.36295/asro.2019.22072.

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de Araújo, Rodrigo Santos Aquino, Vitória Gaspar Bernardo, Robert da Silva Tibúrcio, Danilo Cesar Galindo Bedor, Michel Leandro de Campos, Roberto Pontarolo, Julyanne Maria Saraiva de Sousa et al. "2-Aminothiophene Derivatives—New Drug Candidates Against Leishmaniasis: Drug Design, Synthesis, Pharmacomodulation, and Antileishmanial Activity". Pharmaceuticals 18, n. 1 (17 gennaio 2025): 125. https://doi.org/10.3390/ph18010125.

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Background/Objectives: Leishmaniasis is one of the 20 Neglected Tropical Diseases according to the WHO, affecting approximately 12 million people in four continents, generating serious public health problems. The lack of therapeutic options, associated with toxicity and the emergence of resistance to the few available drugs, makes it urgent to develop new drug options. In this context, the aims of this work are to expand the knowledge about the pharmacophore group responsible for the antileishmanial potential of 2-aminothiophene derivatives. Thus, new compounds were synthesized containing chemical modifications at the C-3, C-4, and C-5 positions of the 2-aminothiophene ring, in addition to the S-Se bioisosterism. Methods: Dozens of 2-AT and 2-aminoselenophen (2-AS) derivatives were sequentially synthesized through applications of the Gewald reaction and were then evaluated in vitro for their activities against L. amazonensis and for cytotoxicity against macrophages. Results: Several series of compounds were synthesized, and it was possible to identify some substitution patterns favorable to the activity generating compounds with IC50 values below 10 µM, such as the non-essentiality of the presence of a carbonitrile group at C-3; the importance of the presence and size of cycloalkyl/piperidinyl chains at C-4 and C-5 in modulating the activity; and the increase in activity without affecting the safety of the S/Se bioisosteric substitution. Conclusions: Taken together, these findings reaffirm the great potential of 2-aminothiophenes to generate antileishmanial drug candidates and offers contributions to the drug design of compounds with an even more promising profile for the problem of leishmaniasis.

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Lesire, Laetitia, Florence Leroux, Rebecca Deprez-Poulain e Benoit Deprez. "Insulin-Degrading Enzyme, an Under-Estimated Potential Target to Treat Cancer?" Cells 11, n. 7 (5 aprile 2022): 1228. http://dx.doi.org/10.3390/cells11071228.

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Insulin-degrading enzyme (IDE) is a multifunctional protease due to the variety of its substrates, its various cellular locations, its conservation between species and its many non-proteolytic functions. Numerous studies have successfully demonstrated its implication in two main therapeutic areas: metabolic and neuronal diseases. In recent years, several reports have underlined the overexpression of this enzyme in different cancers. Still, the exact role of IDE in the physiopathology of cancer remains to be elucidated. Known as the main enzyme responsible for the degradation of insulin, an essential growth factor for healthy cells and cancer cells, IDE has also been shown to behave like a chaperone and interact with the proteasome. The pharmacological modulation of IDE (siRNA, chemical compounds, etc.) has demonstrated interesting results in cancer models. All these results point towards IDE as a potential target in cancer. In this review, we will discuss evidence of links between IDE and cancer development or resistance, IDE’s functions, catalytic or non-catalytic, in the context of cell proliferation, cancer development and the impact of the pharmacomodulation of IDE via cancer therapeutics.

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Dogné, J. M., X. de Leval, P. Neven, S. Rolin, J. Wouters, J. Delarge e B. Masereel. "Pharmacomodulation Studies of Torasemide Leading to Original Non-carboxylic Thromboxane A₂ Receptor Antagonists". Pharmacy and Pharmacology Communications 6, n. 2 (1 febbraio 2000): 77–82. http://dx.doi.org/10.1211/146080800128735674.

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Chollet, Constance, Karolin Meyer e Annette G. Beck-Sickinger. "Ghrelin-a novel generation of anti-obesity drug: design, pharmacomodulation and biological activity of ghrelin analogues". Journal of Peptide Science 15, n. 11 (29 settembre 2009): 711–30. http://dx.doi.org/10.1002/psc.1177.

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Degotte, Gilles, Michel Frederich, Pierre Francotte, Thierry Franck, Thomas Colson, Didier Serteyn e Ange Mouithys-Mickalad. "Targeting Myeloperoxidase Activity and Neutrophil ROS Production to Modulate Redox Process: Effect of Ellagic Acid and Analogues". Molecules 28, n. 11 (2 giugno 2023): 4516. http://dx.doi.org/10.3390/molecules28114516.

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Malaria is an infectious disease caused by a Plasmodium genus parasite that remains the most widespread parasitosis. The spread of Plasmodium clones that are increasingly resistant to antimalarial molecules is a serious public health problem for underdeveloped countries. Therefore, the search for new therapeutic approaches is necessary. For example, one strategy could consist of studying the redox process involved in the development of the parasite. Regarding potential drug candidates, ellagic acid is widely studied due to its antioxidant and parasite-inhibiting properties. However, its low oral bioavailability remains a concern and has led to pharmacomodulation and the synthesis of new polyphenolic compounds to improve antimalarial activity. This work aimed at investigating the modulatory effect of ellagic acid and its analogues on the redox activity of neutrophils and myeloperoxidase involved in malaria. Overall, the compounds show an inhibitory effect on free radicals as well as on the enzyme horseradish peroxidase- and myeloperoxidase (HRP/MPO)-catalyzed oxidation of substrates (L-012 and Amplex Red). Similar results are obtained with reactive oxygen species (ROS) produced by phorbol 12-mystate acetate (PMA)-activated neutrophils. The efficiency of ellagic acid analogues will be discussed in terms of structure–activity relationships.

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Urgin, Karène, Mouhamad Jida, Katharina Ehrhardt, Tobias Müller, Michael Lanzer, Louis Maes, Mourad Elhabiri e Elisabeth Davioud-Charvet. "Pharmacomodulation of the Antimalarial Plasmodione: Synthesis of Biaryl- and N-Arylalkylamine Analogues, Antimalarial Activities and Physicochemical Properties". Molecules 22, n. 1 (19 gennaio 2017): 161. http://dx.doi.org/10.3390/molecules22010161.

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MOUSSAVI, Z., P. DEPREUX, D. LESIEUR, N. COTELLE, J. SAUZIERES, M. O. PLANCKE e J. C. FRUCHART. "ChemInform Abstract: Pharmacomodulation of 7-(2-Methylenebutyryl)-2,3-dihydrobenzoxazin-(1, 4)-3-one Structure and Normolipemic Activity." ChemInform 22, n. 44 (22 agosto 2010): no. http://dx.doi.org/10.1002/chin.199144214.

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Loiseau, Philippe M., Sébastien Pomel e Simon L. Croft. "Chitosan Contribution to Therapeutic and Vaccinal Approaches for the Control of Leishmaniasis". Molecules 25, n. 18 (9 settembre 2020): 4123. http://dx.doi.org/10.3390/molecules25184123.

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The control of leishmaniases, a complex parasitic disease caused by the protozoan parasite Leishmania, requires continuous innovation at the therapeutic and vaccination levels. Chitosan is a biocompatible polymer administrable via different routes and possessing numerous qualities to be used in the antileishmanial strategies. This review presents recent progress in chitosan research for antileishmanial applications. First data on the mechanism of action of chitosan revealed an optimal in vitro intrinsic activity at acidic pH, high-molecular-weight chitosan being the most efficient form, with an uptake by pinocytosis and an accumulation in the parasitophorous vacuole of Leishmania-infected macrophages. In addition, the immunomodulatory effect of chitosan is an added value both for the treatment of leishmaniasis and the development of innovative vaccines. The advances in chitosan chemistry allows pharmacomodulation on amine groups opening various opportunities for new polymers of different size, and physico-chemical properties adapted to the chosen routes of administration. Different formulations have been studied in experimental leishmaniasis models to cure visceral and cutaneous leishmaniasis, and chitosan can act as a booster through drug combinations with classical drugs, such as amphotericin B. The various architectural possibilities given by chitosan chemistry and pharmaceutical technology pave the way for promising further developments.

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Du Preez, Stanley, Natalie Eaton-Fitch, Helene Cabanas, Donald Staines e Sonya Marshall-Gradisnik. "Characterization of IL-2 Stimulation and TRPM7 Pharmacomodulation in NK Cell Cytotoxicity and Channel Co-Localization with PIP2 in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients". International Journal of Environmental Research and Public Health 18, n. 22 (12 novembre 2021): 11879. http://dx.doi.org/10.3390/ijerph182211879.

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Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex multisystemic disorder responsible for significant disability. Although a unifying etiology for ME/CFS is uncertain, impaired natural killer (NK) cell cytotoxicity represents a consistent and measurable feature of this disorder. Research utilizing patient-derived NK cells has implicated dysregulated calcium (Ca2+) signaling, dysfunction of the phosphatidylinositol-4,5-bisphosphate (PIP2)-dependent cation channel, transient receptor potential melastatin (TRPM) 3, as well as altered surface expression patterns of TRPM3 and TRPM2 in the pathophysiology of ME/CFS. TRPM7 is a related channel that is modulated by PIP2 and participates in Ca2+ signaling. Though TRPM7 is expressed on NK cells, the role of TRPM7 with IL-2 and intracellular signaling mechanisms in the NK cells of ME/CFS patients is unknown. This study examined the effect of IL-2 stimulation and TRPM7 pharmacomodulation on NK cell cytotoxicity using flow cytometric assays as well as co-localization of TRPM7 with PIP2 and cortical actin using confocal microscopy in 17 ME/CFS patients and 17 age- and sex-matched healthy controls. The outcomes of this investigation are preliminary and indicate that crosstalk between IL-2 and TRMP7 exists. A larger sample size to confirm these findings and characterization of TRPM7 in ME/CFS using other experimental modalities are warranted.

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Marshall-Gradisnik, Sonya, Etianne Martini Sasso, Natalie Eaton-Fitch, Peter Smith, James N. Baraniuk e Katsuhiko Muraki. "Novel characterization of endogenous transient receptor potential melastatin 3 ion channels from Gulf War Illness participants". PLOS ONE 19, n. 6 (25 giugno 2024): e0305704. http://dx.doi.org/10.1371/journal.pone.0305704.

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Abstract (sommario):

Gulf War Illness (GWI) is a chronic condition characterized by multisystem symptoms that still affect up to one-third of veterans who engaged in combat in the Gulf War three decades ago. The aetiology of GWI is mainly explained by exposure to multiple toxic agents, vaccines, and medications. As there is a significant overlap in symptoms between GWI and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), the objective of this study was to investigate a biomarker widely reported in Natural Killer (NK) cells from ME/CFS patients, the Transient Receptor Potential Melastatin 3 (TRPM3) ion channel. NK cells from 6 healthy controls (HC) and 6 GWI participants were isolated, and TRPM3 function was assessed through whole-cell patch-clamp. As demonstrated by prior studies, NK cells from HC expressed typical TRPM3 function after pharmacomodulation. In contrast, this pilot investigation demonstrates a dysfunctional TRPM3 in NK cells from GWI participants through application of a TRPM3 agonist and confirmed by a TRPM3 antagonist. There was a significant reduction in TRPM3 function from GWI than results measured in HC. This study provides an unprecedented research field to investigate the involvement of TRP ion channels in the pathomechanism and potential medical interventions to improve GWI quality of life.

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Sinyeue, Cynthia, Mariko Matsui, Michael Oelgemöller, Frédérique Bregier, Vincent Chaleix, Vincent Sol e Nicolas Lebouvier. "Synthesis and Investigation of Flavanone Derivatives as Potential New Anti-Inflammatory Agents". Molecules 27, n. 6 (9 marzo 2022): 1781. http://dx.doi.org/10.3390/molecules27061781.

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Flavonoids are polyphenols with broad known pharmacological properties. A series of 2,3-dihydroflavanone derivatives were thus synthesized and investigated for their anti-inflammatory activities. The target flavanones were prepared through cyclization of 2′-hydroxychalcone derivatives, the later obtained by Claisen–Schmidt condensation. Since nitric oxide (NO) represents an important inflammatory mediator, the effects of various flavanones on the NO production in the LPS-induced RAW 264.7 macrophage were assessed in vitro using the Griess test. The most active compounds were flavanone (4G), 2′-carboxy-5,7-dimethoxy-flavanone (4F), 4′-bromo-5,7-dimethoxy-flavanone (4D), and 2′-carboxyflavanone (4J), with IC50 values of 0.603, 0.906, 1.030, and 1.830 µg/mL, respectively. In comparison, pinocembrin achieved an IC50 value of 203.60 µg/mL. Thus, the derivatives synthesized in this work had a higher NO inhibition capacity compared to pinocembrin, demonstrating the importance of pharmacomodulation to improve the biological potential of natural molecules. SARs suggested that the use of a carboxyl-group in the meta-position of the B-ring increases biological activity, whereas compounds carrying halogen substituents in the para-position were less active. The addition of methoxy-groups in the meta-position of the A-ring somewhat decreased the activity. This study successfully identified new bioactive flavanones as promising candidates for the development of new anti-inflammatory agents.

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37

Villa, P., G. Sartor, M. Angelini, M. Sironi, M. Conni, P. Gnocchi, A. M. Isetta, G. Grau, W. Buurman e L. J. van Tits. "Pattern of cytokines and pharmacomodulation in sepsis induced by cecal ligation and puncture compared with that induced by endotoxin." Clinical and diagnostic laboratory immunology 2, n. 5 (1995): 549–53. http://dx.doi.org/10.1128/cdli.2.5.549-553.1995.

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38

Pedron, Julien, Clotilde Boudot, Sandra Bourgeade-Delmas, Alix Sournia-Saquet, Lucie Paloque, Maryam Rastegari, Mansour Abdoulaye et al. "Antitrypanosomatid Pharmacomodulation at Position 3 of the 8-Nitroquinolin-2(1H )-one Scaffold Using Palladium-Catalysed Cross-Coupling Reactions". ChemMedChem 13, n. 20 (17 settembre 2018): 2217–28. http://dx.doi.org/10.1002/cmdc.201800456.

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39

Vidaillac, Céline, Jean Guillon, Corinne Arpin, Isabelle Forfar-Bares, Boubakar B. Ba, Jean Grellet, Stéphane Moreau, Daniel-Henri Caignard, Christian Jarry e Claudine Quentin. "Synthesis of Omeprazole Analogues and Evaluation of These as Potential Inhibitors of the Multidrug Efflux Pump NorA of Staphylococcus aureus". Antimicrobial Agents and Chemotherapy 51, n. 3 (13 novembre 2006): 831–38. http://dx.doi.org/10.1128/aac.01306-05.

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ABSTRACT A series of 11 pyrrolo[1,2-a]quinoxaline derivatives, 1a to 1k, sharing structural analogies with omeprazole, a eukaryotic efflux pump inhibitor (EPI) used as an antiulcer agent, was synthesized. Their inhibitory effect was evaluated using Staphylococcus aureus strain SA-1199B overexpressing NorA. By determinations of the MIC of norfloxacin in the presence of these EPIs devoid of intrinsic antibacterial activity and used at 128 μg/ml, and by the checkerboard method, compound 1e (MIC decrease, 16-fold; fractional inhibitory concentration index [ΣFIC], 0.18) appeared to be more active than compounds 1b to 1d, reserpine, and omeprazole (MIC decrease, eightfold; ΣFIC, 0.31), followed by compounds 1a and 1f (MIC decrease, fourfold; ΣFIC, 0.37) and 1g to 1k (MIC decrease, twofold; ΣFIC, 0.50 to 0.56). By time-kill curves combining norfloxacin (1/4 MIC) and the most efficient EPIs (128 μg/ml), compound 1e persistently restored the bactericidal activity of norfloxacin (inoculum reduction, 3 log10 CFU/ml at 8 and 24 h), compound 1f led to a delayed but progressive decrease in the number of viable cells, and compounds 1b to 1d and omeprazole acted synergistically (inoculum reduction, 3 log10 CFU/ml at 8 h but further regrowth), while compound 1a and reserpine slightly enhanced norfloxacin activity. The bacterial uptake of norfloxacin monitored by high-performance liquid chromatography confirmed that compounds 1a to 1f increased antibiotic accumulation, as did reserpine and omeprazole. Since these EPIs did not disturb the Δψ and ΔpH, they might directly interact with the pump. A structure-activity relationships study identified the benzimidazole nucleus of omeprazole as the main structural element involved in efflux pump inhibition and highlighted the critical role of the chlorine substituents in the stability and efficiency of compounds 1e to 1f. However, further pharmacomodulation is required to obtain therapeutically applicable derivatives.

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Chua, Sarah, Li-Teh Chang, Cheuk-Kwan Sun, Jiunn-Jye Sheu, Fan-Yen Lee, Ali A. Youssef, Cheng-Hsu Yang, Chiung-Jen Wu e Hon-Kan Yip. "Time Courses of Subcellular Signal Transduction and Cellular Apoptosis in Remote Viable Myocardium of Rat Left Ventricles Following Acute Myocardial Infarction: Role of Pharmacomodulation". Journal of Cardiovascular Pharmacology and Therapeutics 14, n. 2 (26 marzo 2009): 104–15. http://dx.doi.org/10.1177/1074248409332841.

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41

Kamso, Viviane Flore Kamlo, Christophe Colombe Simo Fotso, Ines Michèle Kanko Mbekou, Billy Tchegnitegni Tousssie, Bruno Ndjakou Lenta, Fabrice Fekam Boyom, Norbert Sewald, Marcel Frese, Bonaventure Tchaleu Ngadjui e Ghislain Wabo Fotso. "Chemical Constituents of Macaranga occidentalis, Antimicrobial and Chemophenetic Studies". Molecules 27, n. 24 (12 dicembre 2022): 8820. http://dx.doi.org/10.3390/molecules27248820.

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Medicinal plants are known as sources of potential antimicrobial compounds belonging to different classes. The aim of the present work was to evaluate the antimicrobial potential of the crude extract, fractions, and some isolated secondary metabolites from the leaves of Macaranga occidentalis, a Cameroonian medicinal plant traditionally used for the treatment of microbial infections. Repeated column chromatography of the ethyl acetate and n-butanol fractions led to the isolation of seventeen previously known compounds (1−17), among which three steroids (1−3), one triterpene (4), four flavonoids (5−8), two stilbenoids (9 and 10) four ellagic acid derivatives (11−14), one geraniinic acid derivative (15), one coumarine (16), and one glyceride (17). Their structures were elucidated mainly by means of extensive spectroscopic and spectrometric (1D and 2D NMR and, MS) analysis and comparison with the published data. The crude extract, fractions, and isolated compounds were all screened for their antimicrobial activity. None of the natural compounds was active against Candida strains. However, the crude extract, fractions, and compounds showed varying levels of antibacterial properties against at least one of the tested bacterial strains, with minimal inhibitory concentrations (MICs) ranging from 250 to 1000 μg/mL. The n-butanol (n-BuOH) fraction was the most active against Escherichia coli ATCC 25922, with an MIC value of 250 μg/mL. Among the isolated compounds, schweinfurthin B (10) exhibited the best activity against Staphylococcus aureus NR 46003 with a MIC value of 62.5 μg/mL. In addition, schweinfurthin O (9) and isomacarangin (6) also exhibited moderate activity against the same strain with a MIC value of 125 μg/mL. Therefore, pharmacomodulation was performed on compound 6 and three new semisynthetic derivatives (6a–c) were prepared by allylation and acetylation reactions and screened for their in vitro antimicrobial activity. None of the semisynthetic derivatives showed antimicrobial activity against the same tested strains. The chemophenetic significance of the isolated compounds is also discussed in this paper.

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42

HELISSEY, Philippe, Sylviane GIORGI-RENAULT, Jean RENAULT e Suzanne CROS. "Heterocyclic quinones. XIV. Pharmacomodulation in a series of 11H-indolo(3,2-c)quinolinediones: Synthesis and cytotoxicity of 8-substituted 11H-indolo(3,2-c)quinoline-7,10-diones." CHEMICAL & PHARMACEUTICAL BULLETIN 37, n. 3 (1989): 675–79. http://dx.doi.org/10.1248/cpb.37.675.

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43

Sung, Pei-Hsun, Ben-Chung Cheng, Tsuen-Wei Hsu, John Y. Chiang, Hsin-Ju Chiang, Yi-Ling Chen, Chih-Chao Yang e Hon-Kan Yip. "Oxidized-LDL Deteriorated the Renal Residual Function and Parenchyma in CKD Rat through Upregulating Epithelial Mesenchymal Transition and Extracellular Matrix-Mediated Tubulointerstitial Fibrosis—Pharmacomodulation of Rosuvastatin". Antioxidants 11, n. 12 (15 dicembre 2022): 2465. http://dx.doi.org/10.3390/antiox11122465.

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This study tested the hypothesis that intrarenal arterial transfusion of oxidized low-density lipoprotein (ox-LDL) jeopardized the residual renal function and kidney architecture in rat chronic kidney disease ((CKD), i.e., induced by 5/6 nephrectomy) that was reversed by rosuvastatin. Cell culture was categorized into A1 (NRK-52E cells), A2 (NRK-52E + TGF-β), A3 (NRK-52E + TGF-β + ox-LDL) and A4 (NRK-52E + TGF-β + ox-LD). The result of in vitro study showed that cell viability (at 24, 48 and 72 h), NRK-52E ox-LDL-uptake, protein expressions of epithelial–mesenchymal–transition (EMT) markers (i.e., p-Smad2/snail/α-SMA/FSP1) and cell migratory and wound healing capacities were significantly progressively increased from A1 to A4 (all p < 0.001). SD rats were categorized into group 1 (sham-operated control), group 2 (CKD), group 3 (CKD + ox-LDL/0.2 mg/rat at day 14 after CKD induction) and group 4 (CKD + ox-LDL-treated as group 3+ rosuvastatin/10 mg/kg/day by days 20 to 42 after CKD induction) and kidneys were harvested at day 42. The circulatory levels of BUN and creatinine, ratio of urine-protein to urine-creatinine and the protein expressions of the above-mentioned EMT, apoptotic (cleaved-caspase3/cleaved-PARP/mitochondrial-Bax) and oxidative-stress (NOX-1/NOX-2/oxidized-protein) markers were lowest in group 1, highest in group 3 and significantly higher in group 4 than in group 2 (all p < 0.0001). Histopathological findings demonstrated that the kidney injury score, fibrotic area and kidney injury molecule-1 (KIM-1) displayed an identical pattern, whereas the cellular expression of podocyte components (ZO-1/synaptopodin) exhibited an opposite pattern of EMT markers (all p < 0.0001). In conclusion, ox-LDL damaged the residual renal function and kidney ultrastructure in CKD mainly through augmenting oxidative stress, EMT and fibrosis that was remarkably reversed by rosuvastatin.

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44

Lee, Fan-Yen, Mel S. Lee, Christopher Glenn Wallace, Chi-Ruei Huang, Chi-Hsiang Chu, Zhi-Hong Wen, Jhih-Hong Huang, Xue-Sheng Chen, Chia C. Wang e Hon-Kan Yip. "Short-interval exposure to ambient fine particulate matter (PM2.5) exacerbates the susceptibility of pulmonary damage in setting of lung ischemia-reperfusion injury in rodent: Pharmacomodulation of melatonin". Biomedicine & Pharmacotherapy 113 (maggio 2019): 108737. http://dx.doi.org/10.1016/j.biopha.2019.108737.

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45

Gnoatto, Simone C. B., Sophie Susplugas, Luciana Dalla Vechia, Thais B. Ferreira, Alexandra Dassonville-Klimpt, Karine R. Zimmer, Catherine Demailly et al. "Pharmacomodulation on the 3-acetylursolic acid skeleton: Design, synthesis, and biological evaluation of novel N-{3-[4-(3-aminopropyl)piperazinyl]propyl}-3-O-acetylursolamide derivatives as antimalarial agents". Bioorganic & Medicinal Chemistry 16, n. 2 (gennaio 2008): 771–82. http://dx.doi.org/10.1016/j.bmc.2007.10.031.

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46

Legeay, Samuel, Kien Trân, Yannick Abatuci, Hélène Justiniano, Claire Lugnier, Olivier Duval, Jean-Jacques Helesbeux e Sébastien Faure. "Design, Synthesis, Pharmacological Evaluation and Vascular Effects of Delphinidin Analogues". Current Pharmaceutical Design 24, n. 46 (26 aprile 2019): 5580–89. http://dx.doi.org/10.2174/1381612825666190206144913.

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Abstract (sommario):

Background: Among polyphenolic compounds suggested to prevent cardiovascular diseases (CVDs) and to explain the “French paradox”, the anthocyanidin delphinidin (Dp) has been reported to support at least partly the vascular beneficial effects of dietary polyphenolic compounds including those from fruits and related products as red wine. It has also been highlighted that Dp interacts directly with the active site of estrogen receptor α (ERα), leading to activation of endothelial NO synthase (eNOS) pathway thus contributing to the prevention of endothelial dysfunction in mice aorta. However, anthocyanidins have very low bioavailability and despite a well described in vitro efficacy, the very high hydrophilicity and physicochemical instability of Dp might explain the lack of in vivo reported effects. Objective: The aim of this study was to identify new Dp analogues with increased lipophilicity and vasorelaxation potential by a chemical modulation of its structure and to characterize the signaling pathway notably in relation with ERα signaling and nitric oxide (NO) production. Method: OCH3-substituted delphinidin analogues were obtained through the coupling of the corresponding acetophenones with substituted benzaldehydes. Prediction of resorption of the flavylium derivatives was performed with the calculated logP and induction of vasorelaxation was performed by myography on WT and ERαKO mice thoracic aorta rings and compared to Dp. NO production was evaluated in vitro on human primary endothelial cells. Results: Eight Dp analogues were synthesized including four new flavylium derivatives. Two compounds (9 and 11) showed a strong increase of vasorelaxation potential and a theoretically increased bioavailability compared to Dp. Interestingly, 9 and 11 induced increased O2 - or NO endothelial production respectively and revealed a novel NO-dependent ERα-independent relaxation compared to Dp. We suggested that this mechanism may be at least in part supported by the inhibition of vascular cyclic nucleotide phosphodiesterase (PDEs). Conclusion: The current study demonstrated that pharmacomodulation of the Dp backbone by replacement of OH groups by OCH3 groups of the A and B rings led to the identification and characterization of two compounds (9 and 11) with enhanced physio-chemical properties that could be associated to higher permeability capability and pharmacological activity for the prevention of CVDs compared to Dp.

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Karkischenko, N. N., V. N. Karkischenko e Yu V. Fokin. "Mechanisms of the Pharmacological Modulation of Obsessive-Compulsive and Cognitive Disorders in Cats Recognized by the Method of Normalizing FFT-Convertible Functions of Electrograms of the Frontal Cortex and Hippocampus". Journal Biomed 16, n. 1 (28 febbraio 2020): 12–27. http://dx.doi.org/10.33647/2074-5982-16-1-12-27.

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Abstract (sommario):

The pharmacological modulation and analysis of psychopathological processes in animals is a research method providing a possibility to study similar processes in humans. Methods and approaches based on the principles of the pharmacological modulation of systemic behaviour and normalization of FFT-transformed functions of the brain electrograms allow identiﬁcation of the quantitative parameters of intracentral relations, cognitive functions and fundamental mechanisms for evaluating the effects of neuropsychoactive drugs in the whole brain in vivo.The work was carried out on cats with stereotactically implanted electrodes in the brain. Subtherapeutic doses of ketamine, amphetamine and nakom were used to model obsessive-compulsive disorders and cognitive changes. The pharmacological modulation of the animals’ behaviour was evaluated by the effect on the frontal brain and hippocampus. The activation of γ-rhythms (from 35 to 60 Hz) was considered as an improvement in cognitive functions. Ketamine exhibited a more pronounced depressing effect on the proreal gyrus, with its activating effects being close to amphetamine across the frequency ranges of 11–15 and 32–35 Hz. Ketamine had a pronounced activating effect on the gyrus suprasilvium anterior and the hippocampus. Ketamin and nakom demonstrated similar effects in the area of the proreal gyrus, most clearly manifested at frequencies of about 9–15 and 35–36 Hz. The action of nakom was characterized by the episodes of activation in a higher frequency range of 40–55 Hz as well. In the area of the gyrus suprasilvium anterior, the effects of nakom were similar to those of ketamine; however, these substances exhibited different effects in the range of 9–11 Hz. Compared to amphetamine, nakom showed no depressing episodes over the high-frequency range of 55–65 Hz. In the hippocampus, nakom demonstrated an activating effect exceeding that of ketamine by 100–150%. It was shown that neuroimaging of the normalized functions of electrograms during the pharmacological modulation of obsessive-compulsive and cognitive disorders reﬂects the most striking transformations in high-frequency brain rhythms, primarily related to the γ-range.Comparison of the results of pharmacomodulation with the pharmacodynamic and pharmacokinetic parameters of drugs when modelling psychopathologies in animals helps researchers in their search for approaches to modifying animal behaviour and extrapolating them to humans.

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Deau, Emmanuel, Elodie Robin, Raluca Voinea, Nathalie Percina, Grzegorz Satała, Adriana-Luminita Finaru, Agnès Chartier et al. "Rational Design, Pharmacomodulation, and Synthesis of Dual 5-Hydroxytryptamine 7 (5-HT7)/5-Hydroxytryptamine 2A (5-HT2A) Receptor Antagonists and Evaluation by [18F]-PET Imaging in a Primate Brain". Journal of Medicinal Chemistry 58, n. 20 (5 ottobre 2015): 8066–96. http://dx.doi.org/10.1021/acs.jmedchem.5b00874.

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49

HELISSEY, Phillippe, Sylviane GIORGI-RENAULT, Jean RENAULT e Suzanne CROS. "Heterocyclic quinones. XVI. Pharmacomodulation in the series of 11H-indolo(3,2-c)quinolinediones: Synthesis, cytotoxicity and antitumor activity of 3-substituted 11H-pyrido(3',4':4,5)pyrrolo(3,2-c)quinoline-1,4-diones." CHEMICAL & PHARMACEUTICAL BULLETIN 37, n. 9 (1989): 2413–16. http://dx.doi.org/10.1248/cpb.37.2413.

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50

Briday, Mathilde, François Hallé, Lauriane Lecoq, Sylvie Radix, Juliette Martin, Roland Montserret, Marie Dujardin et al. "Pharmacomodulation of a ligand targeting the HBV capsid hydrophobic pocket". Chemical Science, 2022. http://dx.doi.org/10.1039/d2sc02420a.

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Hepatitis B virus (HBV) is a small enveloped retrotranscribing DNA virus and an important human pathogen. Its capsid-forming core protein (Cp) features a hydrophobic pocket proposed to be central notably...

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