Journal articles: 'SILICO STUDIES'

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Semenyuta, I. V., O. P. Trokhimenko, I. V. Dziublyk, S. O. Soloviov, V. V. Trokhymchuk, O. L. Bororova, D. M. Hodyna, M. P. Smetiukh, O. K. Yakovenko, and L. О. Metelytsia. "Decamethoxin virucidal activity: in vitro and in silico studies." Ukrainian Biochemical Journal 94, no. 3 (October 4, 2022): 81–91. http://dx.doi.org/10.15407/ubj94.03.081.

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The data on the representative of decamethoxin short-term action on infectious bronchitis virus (IBV) strain H120 used as a human-safe model of SARS-CoV-2 virus are presented. The viral activity was estimated with the use of inverted microscope PrimoVert (Germany) by destructive effect on BHK21 fibroblastic cell line. In vitro results demonstrated that decamethoxin (100 μg/ml) completely inactivated IBV coronavirus strain at exposure of 30 sec and more. At the lowest decamethoxin exposure of 10 sec the antiseptic virucidal activity was 33% and 36% of control at 24 and 48 h of cultivation respectively. Molecular docking analysis indicated the significant similarity of IBV and SARS-CoV-2 main protease (Mpro) structure. Docking studies of decamethoxin interaction with IBV Mpro and SARS-CoV-2 Mpro active centers demonstrated the ligand-protein complexes formation with the estimated binding energy of -8.6, -8.4 kcal/mol and key amino acid residues ASN26, GLY141, GLU187, GLU164, THR24, THR25, ASN142, GLY143, CYS145, HIS164 and GLU166. Keywords: decamethoxin, IBV strain H120, main protease, molecular docking, QAC, SARS-COV-2, virucidal activity

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Ramakrishnan, Gautham Subramaniam, Manali Mukund Kamath, and Vidya Niranjan. "Increasing Microbial Biofuel Production by In-silico Comparative Genomic Studies." International Journal of Bioscience, Biochemistry and Bioinformatics 4, no. 5 (2014): 386–90. http://dx.doi.org/10.7763/ijbbb.2014.v4.375.

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de Brevern, Alexandre, Ludovic Autin, Yves Colin, Olivier Bertrand, and Catherine Etchebest. "In Silico Studies on DARC." Infectious Disorders - Drug Targets 9, no. 3 (June 1, 2009): 289–303. http://dx.doi.org/10.2174/1871526510909030289.

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Mekapothula, Subbareddy, A. D. Dinga Wonanke, Matthew A. Addicoat, John D. Wallis, David J. Boocock, and Gareth W. V. Cave. "A supramolecular cavitand for selective chromatographic separation of peptides using LC-MS/MS: a combined in silico and experimental approach." New Journal of Chemistry 45, no. 1 (2021): 141–46. http://dx.doi.org/10.1039/d0nj03555f.

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The chromatographic separation of proteomic standards via a silica immobilized pillararene cavitand has been designed in silico using host–guest binding energy studies and realized experimentally to selectively interact with peptides.

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Ekerendu, Effiong E., Uchechukwu C. Okoro, Cosmas C. Eze, David S. Khanye, Kingsley O. Omeje, Narendra K. Mishra, and David I. Ugwu. "Novel Cholinesterase Inhibitors: Synthesis, in silico and in vitro Studies." Asian Journal of Chemistry 35, no. 7 (2023): 1683–91. http://dx.doi.org/10.14233/ajchem.2023.27588.

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The synthesis of new functionalized linear diaza and triaza phenothiazine and phenoxazines and their in silico and in vitro anti-Alzheimer activity is reported. Fifteen new amide derivatives (8-11 & 13-24) were synthesized by the reactions of phenothiazines/phenoxazine (6 or 12) and various aliphatic and aromatic primary amides (7) in the presence of nickel catalyst and anhydrous potassium carbonate under nitrogen atmosphere. The FTIR, 1H NMR, 13C NMR and HR-MS spectra of the synthesized compounds were in agreement with the assigned structures. All the 15 new derivatives were screened for their in silico and in vitro anti-Alzheimer’s activity using the inhibition of acetylcholinesterase and butyrylcholinesterase. The results of the in silico experiment showed that most of the synthesized derivatives had good binding energies, binding interaction and bond distances. The most active derivatives in the in silico studies was compounds 18 (-12.5 and -11.5 kcal/mol) against acetylcholinesterase and butyrylcholinesterase, respectively. In addition, compound 18 had the best in vitro inhibitory activity against acetylcholinesterase and butyrylcholinesterase (99.37% and 82.35%). The results of in silico experiment were greatly in agreement with the results of in vitro studies. The structure-activity relationship studies revealed that the phenothiazine derivatives had better in silico and in vitro activities. Furthermore, 2-substitutted phenothiazines had better activity than the unsubstituted phenothiazines. The synthesized compounds showed promising in silico and in vitro activities against acetylcholinesterase and butyrylcholinesterase and as such could be further developed for the treatment of Alzheimer’s disease.

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Sanchez-Flores, Alejandro. "A 'clap' for in silico studies." Nature Reviews Microbiology 9, no. 1 (December 16, 2010): 7. http://dx.doi.org/10.1038/nrmicro2496.

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Rimola, Albert, Mariona Sodupe, and Piero Ugliengo. "Role of Mineral Surfaces in Prebiotic Chemical Evolution. In Silico Quantum Mechanical Studies." Life 9, no. 1 (January 17, 2019): 10. http://dx.doi.org/10.3390/life9010010.

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There is a consensus that the interaction of organic molecules with the surfaces of naturally-occurring minerals might have played a crucial role in chemical evolution and complexification in a prebiotic era. The hurdle of an overly diluted primordial soup occurring in the free ocean may have been overcome by the adsorption and concentration of relevant molecules on the surface of abundant minerals at the sea shore. Specific organic–mineral interactions could, at the same time, organize adsorbed molecules in well-defined orientations and activate them toward chemical reactions, bringing to an increase in chemical complexity. As experimental approaches cannot easily provide details at atomic resolution, the role of in silico computer simulations may fill that gap by providing structures and reactive energy profiles at the organic–mineral interface regions. Accordingly, numerous computational studies devoted to prebiotic chemical evolution induced by organic–mineral interactions have been proposed. The present article aims at reviewing recent in silico works, mainly focusing on prebiotic processes occurring on the mineral surfaces of clays, iron sulfides, titanium dioxide, and silica and silicates simulated through quantum mechanical methods based on the density functional theory (DFT). The DFT is the most accurate way in which chemists may address the behavior of the molecular world through large models mimicking chemical complexity. A perspective on possible future scenarios of research using in silico techniques is finally proposed.

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Saldanha, Leonor, Ülo Langel, and Nuno Vale. "In Silico Studies to Support Vaccine Development." Pharmaceutics 15, no. 2 (February 15, 2023): 654. http://dx.doi.org/10.3390/pharmaceutics15020654.

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The progress that has been made in computer science positioned in silico studies as an important and well-recognized methodology in the drug discovery and development process. It has numerous advantages in terms of costs and also plays a huge impact on the way the research is conducted since it can limit the use of animal models leading to more sustainable research. Currently, human trials are already being partly replaced by in silico trials. EMA and FDA are both endorsing these studies and have been providing webinars and guidance to support them. For instance, PBPK modeling studies are being used to gather data on drug interactions with other drugs and are also being used to support clinical and regulatory requirements for the pediatric population, pregnant women, and personalized medicine. This trend evokes the need to understand the role of in silico studies in vaccines, considering the importance that these products achieved during the pandemic and their promising hope in oncology. Vaccines are safer than other current oncology treatments. There is a huge variety of strategies for developing a cancer vaccine, and some of the points that should be considered when designing the vaccine technology are the following: delivery platforms (peptides, lipid-based carriers, polymers, dendritic cells, viral vectors, etc.), adjuvants (to boost and promote inflammation at the delivery site, facilitating immune cell recruitment and activation), choice of the targeted antigen, the timing of vaccination, the manipulation of the tumor environment, and the combination with other treatments that might cause additive or even synergistic anti-tumor effects. These and many other points should be put together to outline the best vaccine design. The aim of this article is to perform a review and comprehensive analysis of the role of in silico studies to support the development of and design of vaccines in the field of oncology and infectious diseases. The authors intend to perform a literature review of all the studies that have been conducted so far in preparing in silico models and methods to support the development of vaccines. From this point, it was possible to conclude that there are few in silico studies on vaccines. Despite this, an overview of how the existing work could support the design of vaccines is described.

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Vasil Lyubenov, Kanistov. "Results of the Application of Pharmacological in Silico Base Structures in Studies of Endothelioprotective Properties of Drugs for The Treatment of Coronavirus Infection (Covid-19)." Pharmacy and Drug Development 1, no. 2 (December 8, 2022): 01–05. http://dx.doi.org/10.58489/2836-2322/008.

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Purpose. Identifying the results of the application in silico of the basic structures, in the study of the endothelial proprotective properties of drugs for the treatment of coronavirus infection (COVID-19), affecting the pharmacological targets of the cardiovascular system (CVS). The article is aimed at researchers in the field of theoretical and experimental pharmacology and medicine. Materials and methods. We accept the physico-mathematical model "damper-spring" as a theoretical and experimental justification for the development of methods for mathematical modeling in silico of basic structures, for studying the endothelioprotective properties of drugs. We introduce theoretical and experimental development in silico of basic structures in the study of endothelioprotective properties of drugs for the treatment of coronavirus infection (COVID-19). Outcomes. Established by the experimental pathway influence of endothelial function and values of cost in silico coefficients and

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Gomes, Andréia Patricia, Brenda Silveira Valles Moreira, Felipe José Dutra Dias, Victor Hiroshi Bastos Inoue, Gabriel Vita Silva Franco, Daniela De Souza Gomes, Alcione De Paiva Oliveira, et al. "Plasmodium Falciparum Infection: In Silico Preliminary Studies." Abakós 5, no. 1 (November 29, 2016): 63. http://dx.doi.org/10.5752/p.2316-9451.2016v5n1p63.

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<div class="page" title="Page 3"><div class="layoutArea"><div class="column">Malaria is an infectious disease of great impact in terms of public health, given the number of people affected and subjected to the risk of illness. Protozoa of the genus Plasmodium cause it and five species can infect humans: Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, Plasmodium malariae and Plasmodium knowlesi; the first is able to produce the most severe cases of the disease. Despite its clinical and epidemiological relevance and investigations in development – targeted at different aspects of the interaction between humans and Plasmodium protozoa of the genus – there remains many questions about different aspects of the malaria pathophysiology. To study such gaps, interdisciplinary strategies can be pursed, which involve biology, medicine an computer science, as part of the trial in silico. Such approach provides agility, low cost and does not imply ethical issues that permeate the experiments in vitro and in vivo. Based on these considerations, this article presents preliminary results of a computational model of the interaction between P. falciparum and erythrocytes, implemented in AutoSimmune system. The results obtained show that the system is able to simulate the host cells infection process by protozoan with similarities with the biological reality. </div></div></div>

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Triveni, S., C. Naresh Babu, E. Bhargav, and M. Vijaya Jyothi. "in silico Design, ADME Prediction, Molecular Docking, Synthesis of Novel Triazoles, Indazoles & Aminopyridines and in vitro Evaluation of Antitubercular Activity." Asian Journal of Chemistry 32, no. 11 (2020): 2713–21. http://dx.doi.org/10.14233/ajchem.2020.22790.

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To design and synthesize novel triazoles, indazoles and aminopyridines from various (thiophene-2-yl)prop-2-en-1-one derivatives as antitubercular leads by in silico and in vitro methods. in silco Drug design, ADME prediction and molecular docking studies were performed to assess drug likeliness and antitubercular potential of all 30 novel triazoles, indazoles and aminopyridines. in silico Drug design studies revealed that the synthetic routes applied were appropriate according to the calculations of Swiss-ADME that measure synthetic accessibility. Most of the synthesized compounds found to have considerable binding score with enoyl ACP reductase enzyme of Mycobacterium tuberculosis. All the synthesized compounds were evaluated for antitubercular potential against Drug Resistant Mycobacterium tuberculosis H37Rv strain by Luciferase reporter assay method. Most of the synthesized compounds exhibited remarkable antitubercular potential against resistant strain.

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Al-Khafaji, Zahra M. "In Silico Investigation of Rv Hypothetical Proteins of Virulent Strain Mycobacterium tuberculosis H37Rv." Indian Journal of Pharmaceutical and Biological Research 1, no. 04 (December 31, 2013): 81–88. http://dx.doi.org/10.30750/ijpbr.1.4.15.

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Tuberculosis is an universal health problem worldwide. In Iraq the problem is aggravated by drug resistance. In Silico studies usually pave the way for more investigations of the real problem .On the other hand Mycobacterium tuberculosis does not lend itself for deep wet lab studies, therefore, In Silico studies must precede many aspects of experimental work. In Silico studies were carried out using most virulent strain and a model of studies M. tuberculosis H37Rv to investigate some of the hypothetical proteins which compromised about 39% of the annotated proteins. The studied Rv hypothetical proteins were distributed among cellular compartment fractions with high existence in the cytoplasmic fraction (about 67%). Major function prediction of these proteins were found in cellular process section using different approaches of predictions .However , some of these proteins were still await to be included in the important databases such as COG and GO which concerned mainly with function annotation.

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Kumar, Anil, Vivian Praveen, and Gangadhar Belavadi. "D-Pencillamine induced nephrotic syndrome in 11-year old girl with wilson disease: A case report." Indian Journal of Pharmaceutical and Biological Research 1, no. 04 (December 31, 2013): 113–15. http://dx.doi.org/10.30750/ijpbr.1.4.20.

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Tuberculosis is an universal health problem worldwide. In Iraq the problem is aggravated by drug resistance. In Silico studies usually pave the way for more investigations of the real problem .On the other hand Mycobacterium tuberculosis does not lend itself for deep wet lab studies, therefore, In Silico studies must precede many aspects of experimental work. In Silico studies were carried out using most virulent strain and a model of studies M. tuberculosis H37Rv to investigate some of the hypothetical proteins which compromised about 39% of the annotated proteins. The studied Rv hypothetical proteins were distributed among cellular compartment fractions with high existence in the cytoplasmic fraction (about 67%). Major function prediction of these proteins were found in cellular process section using different approaches of predictions .However , some of these proteins were still await to be included in the important databases such as COG and GO which concerned mainly with function annotation.

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Sivaraj, Saranya, Gomathi Kannayiram, and Gayathri Dasararaju. "EVALUATION OF ANTI-DIABETIC ACTIVTY OF DIFFERENT EXTRACTS OF MYRISTICA FRAGRANS HOUTT: IN VITRO AND IN SILICO STUDIES." Asian Journal of Pharmaceutical and Clinical Research 10, no. 4 (April 1, 2017): 275. http://dx.doi.org/10.22159/ajpcr.2017.v10i4.16720.

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Objective: This study is aimed to evaluate the anti-diabetic effect of sequentially extracted (hexane, dichloromethane, ethyl acetate, and ethanol) Myristica fragrans houtt (mace) through in vitro and in silico studies. Methods: The in vitro anti-diabetic effect of the sequentially extracted plant were evaluated for its alpha-amylase inhibitory activity and the potential binding was studied by in silico studies using Schrödinger Maestro.Results: All extracts showed dose dependent alpha-amylase inhibitory effect. At concentration 500 µg/ml, all the extracts showed more than 60% inhibition of the alpha-amylase enzyme and the highest inhibition (81.30%) at 500 µg/ml was observed in DCM extract of mace. Potential compounds were identified by in silico molecular docking studies of alpha-amylase with phytocomponents from DCM extract. Among the top three compounds from virtual screening, induced fit docking studies revealed 2,5-bis(3,4-dimethoxyphenyl)-3,4-dimethyloxolane possessed better binding affinity when compared with the drug metformin. Conclusion: The obtained in vitro and in silico results suggest that all extracts of Myristica fragrans can be used successfully for the management of diabetes mellitus.Keywords: Myristica fragrans, Mace, Sequential extraction, Alpha-amylase, Molecular docking.

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Monisha.M, Dr, Dr Abhaya Kumar Mishra, Dr Ramesh N V, Dr K. Unnikrishna Pillai, and Dr Vineeth P K. "In-silico studies in herbal drugs: A review." Journal of Ayurvedic and Herbal Medicine 4, no. 1 (April 3, 2018): 43–47. http://dx.doi.org/10.31254/jahm.2018.4109.

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Bioinformatics is the latest technology in the research field. In-silico studies are done to identify the exact target of the drug. Which finds a drug for the particular binding site and final stage animal testing can be done for obtaining a conform result. Reviews of in-silico studies in herbal drugs were retrieved through the use of PubMed. Specific software on a computer allows researchers to analyse enormous data without actually conducting a large number of experiments. It helps to give the existing information to model disease pathway and identifies precise targets of the selected drugs. Modern instrumental techniques like XRD, XRF, ICP-MS etc. help in quantitative and qualitative estimation of metals and minerals and structural analysis of compound drugs. A later stage in vivo and in vitro studies can be done for obtaining the confirmatory result.

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Mousavi, Sarah, Shima Zare, Mahmoud Mirzaei, and Awat Feizi. "Novel Drug Design for Treatment of COVID-19: A Systematic Review of Preclinical Studies." Canadian Journal of Infectious Diseases and Medical Microbiology 2022 (September 25, 2022): 1–70. http://dx.doi.org/10.1155/2022/2044282.

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Background. Since the beginning of the novel coronavirus (SARS-CoV-2) disease outbreak, there has been an increasing interest in discovering potential therapeutic agents for this disease. In this regard, we conducted a systematic review through an overview of drug development (in silico, in vitro, and in vivo) for treating COVID-19. Methods. A systematic search was carried out in major databases including PubMed, Web of Science, Scopus, EMBASE, and Google Scholar from December 2019 to March 2021. A combination of the following terms was used: coronavirus, COVID-19, SARS-CoV-2, drug design, drug development, In silico, In vitro, and In vivo. A narrative synthesis was performed as a qualitative method for the data synthesis of each outcome measure. Results. A total of 2168 articles were identified through searching databases. Finally, 315 studies (266 in silico, 34 in vitro, and 15 in vivo) were included. In studies with in silico approach, 98 article study repurposed drug and 91 studies evaluated herbal medicine on COVID-19. Among 260 drugs repurposed by the computational method, the best results were observed with saquinavir (n = 9), ritonavir (n = 8), and lopinavir (n = 6). Main protease (n = 154) following spike glycoprotein (n = 62) and other nonstructural protein of virus (n = 45) was among the most studied targets. Doxycycline, chlorpromazine, azithromycin, heparin, bepridil, and glycyrrhizic acid showed both in silico and in vitro inhibitory effects against SARS-CoV-2. Conclusion. The preclinical studies of novel drug design for COVID-19 focused on main protease and spike glycoprotein as targets for antiviral development. From evaluated structures, saquinavir, ritonavir, eucalyptus, Tinospora cordifolia, aloe, green tea, curcumin, pyrazole, and triazole derivatives in in silico studies and doxycycline, chlorpromazine, and heparin from in vitro and human monoclonal antibodies from in vivo studies showed promised results regarding efficacy. It seems that due to the nature of COVID-19 disease, finding some drugs with multitarget antiviral actions and anti-inflammatory potential is valuable and some herbal medicines have this potential.

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Yennamalli, Ragothaman M., Pulkit Anupam Srivastava, Sheena D. Sarswati, and Vijay Kumar Garlapati. "Recombinant Production and Molecular Docking Studies of Casoplatelin, a Bioactive Peptide." Open Biotechnology Journal 14, no. 1 (August 19, 2020): 84–92. http://dx.doi.org/10.2174/1874070702014010084.

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Background: Bioactive peptides from κ-casein have immense therapeutic potential as prophylactic formulations. Among these, casoplatelin is a κ-casein derived bioactive peptide with anti-thrombotic activities. Aim: Herein, we report the production of casoplatelin in an E. coli expression system (using a pBAD vector) and show in silico modeling of its interactions. Methods: A synthetic DNA construct encoding casoplatelin was designed with pepsin cleavage sites before and after the synthetic construct to allow the release of the peptide from the pro-peptide. Results: A novel recombinant approach was demonstrated for the production of casoplatelin, and anti-platelet aggregation activities of the product were confirmed. Also, casoplatelin structures were characterized in silico and then implemented to determine potential structural interactions with fibrinogen. Conclusion: The present study showcases the recombinant approach for biopeptide production and its interaction with fibrinogen through in silico approach.

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Ahmet Harmankaya, Ahmet Harmankaya, Nam k. K. l. n. Nam k K l n, Murat Beytur Murat Beytur, Yonca Y. lmaz Yonca Y lmaz, and Sevda Manap and Haydar Y. ksek Sevda Manap and Haydar Y ksek. "Synthesis, Spectroscopic Analysis, Biological Evaluation, and In Silico Studies of Novel Benzenesulfonate-Derived Schiff-Mannich Bases." Journal of the chemical society of pakistan 45, no. 4 (2023): 323. http://dx.doi.org/10.52568/001280/jcsp/45.04.2023.

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In the current study, 3-formyl phenyl benzenesulfonate is created by reacting 3-hydroxybenzaldehyde with benzene sulfonyl chloride, which is aided by triethylamine. Nine unique (Z)-3-[(3-substituted-5-oxo-1,5-dihydro-4H-1,2,4-triazol-4-yl)-iminomethyl] compounds were formed through the reaction of a manufactured 3-formyl phenyl benzenesulfonate chemical with nine 3-alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-one, as detailed in the existing literature. Phenyl benzene sulfonate (S) compounds were purchased. Through the reaction of the Schiff bases that were made a secondary amine, such as morpholine with formaldehyde, heterocyclic Mannich bases of a unique kind were created. Five recently found (Z)-3-[(3-substituted-5-oxo-1,5-dihydro-4H-1,2,4-triazol-4-yl)-iminomethyl] compounds are presented in this work. By reacting phenyl benzene sulfonate (S) with morpholine in the presence of formaldehyde, five new (Z)-3-[(3-substituted-1-(morpholinomethyl)-5-oxo-1,5-dihydro-4H-1,2,4-triazol-4-yl)-iminomethyl] compounds were created. Chemical compounds fall under the category of phenylbenzene sulfonates (M). Utilizing IR, 1H NMR, and 13C NMR spectroscopy, fourteen recently novel compoundsand#39; chemical structures were examined. The ability of the freshly synthesized Schiff and morpholine-derived Mannich bases to obstruct the acetylcholinesterase enzymeand#39;s (AChE) activity was also assessed. The 1,2,4-triazole functional group was modified by adding various groups at the 1 and 3 positions, resulting in a collection of compounds (S1–9 and M1, 2, 4, 5, 7). It was determined whether these synthetic compounds could prevent the human recombinant AR enzyme from working in vitro, and the findings were validated using molecular docking, molecular mechanics, and ADME analyses. To better understand this mechanism, synthetic Schiff and Mannich base derivatives as well as the positive control substance quercetin were tested using molecular docking against the human recombinant AR enzyme in vitro. To assess the drug-like properties of Schiff and Mannich base analogs, a series of absorption, distribution, metabolism, and excretion (ADME) properties were analyzed theoretically.

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Hdoufane, Ismail, Imane Bjij, Mahmoud Soliman, Alia Tadjer, Didier Villemin, Jane Bogdanov, and Driss Cherqaoui. "In Silico SAR Studies of HIV-1 Inhibitors." Pharmaceuticals 11, no. 3 (July 13, 2018): 69. http://dx.doi.org/10.3390/ph11030069.

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Quantitative Structure Activity Relationships (QSAR or SAR) have helped scientists to establish mathematical relationships between molecular structures and their biological activities. In the present article, SAR studies have been carried out on 89 tetrahydroimidazo[4,5,1-jk][1,4]benzodiazepine (TIBO) derivatives using different classifiers, such as support vector machines, artificial neural networks, random forests, and decision trees. The goal is to propose classification models that will be able to classify TIBO compounds into two groups: high and low inhibitors of HIV-1 reverse transcriptase. Each molecular structure was encoded by 10 descriptors. To check the validity of the established models, all of them were subjected to various validation tests: internal validation, Y-randomization, and external validation. The established classification models have been successful. The correct classification rates reached 100% and 90% in the learning and test sets, respectively. Finally, molecular docking analysis was carried out to understand the interactions between reverse transcriptase enzyme and the TIBO compounds studied. Hydrophobic and hydrogen bond interactions led to the identification of active binding sites. The established models could help scientists to predict the inhibition activity of untested compounds or of novel molecules prior to their synthesis. Therefore, they could reduce the trial and error process in the design of human immunodeficiency virus (HIV) inhibitors.

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Monteiro, Alex F. M., Jessika de Oliveira Viana, Engene Muratov, Marcus T. Scotti, and Luciana Scotti. "In Silico Studies against Viral Sexually Transmitted Diseases." Current Protein & Peptide Science 20, no. 12 (December 16, 2019): 1135–50. http://dx.doi.org/10.2174/1389203720666190311142747.

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Sexually Transmitted Diseases (STDs) refer to a variety of clinical syndromes and infections caused by pathogens that can be acquired and transmitted through sexual activity. Among STDs widely reported in the literature, viral sexual diseases have been increasing in a number of cases globally. This emphasizes the need for prevention and treatment. Among the methods widely used in drug planning are Computer-Aided Drug Design (CADD) studies and molecular docking which have the objective of investigating molecular interactions between two molecules to better understand the three -dimensional structural characteristics of the compounds. This review will discuss molecular docking studies applied to viral STDs, such as Ebola virus, Herpes virus and HIV, and reveal promising new drug candidates with high levels of specificity to their respective targets.

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Lands, Bill. "Lipid nutrition: “In silico” studies and undeveloped experiments." Progress in Lipid Research 85 (January 2022): 101142. http://dx.doi.org/10.1016/j.plipres.2021.101142.

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Ngo, Son Tung, Khanh B. Vu, Minh Quan Pham, Nguyen Minh Tam, and Phuong-Thao Tran. "Marine derivatives prevent w MUS81 in silico studies." Royal Society Open Science 8, no. 9 (September 2021): 210974. http://dx.doi.org/10.1098/rsos.210974.

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The winged-helix domain of the methyl methanesulfonate and ultraviolet-sensitive 81 ( w MUS81) is a potential cancer drug target. In this context, marine fungi compounds were indicated to be able to prevent w MUS81 structure via atomistic simulations. Eight compounds such as D197 ( Tryptoquivaline U ), D220 ( Epiremisporine B ), D67 ( Aspergiolide A ), D153 ( Preussomerin G ), D547 ( 12,13-dihydroxyfumitremorgin C ), D152 ( Preussomerin K ), D20 ( Marinopyrrole B ) and D559 ( Fumuquinazoline K ) were indicated that they are able to prevent the conformation of w MUS81 via forming a strong binding affinity to the enzyme via perturbation approach. The electrostatic interaction is the dominant factor in the binding process of ligands to w MUS81. The residues Trp55, Arg59, Leu62, His63 and Arg69 were found to frequently form non-bonded contacts and hydrogen bonds to inhibitors. Moreover, the influence of the ligand D197 , which formed the lowest binding free energy to w MUS81, on the structural change of enzyme was investigated using replica exchange molecular dynamics simulations. The obtained results indicated that D197 , which forms a strong binding affinity, can modify the structure of w MUS81. Overall, the marine compounds probably inhibit w MUS81 due to forming a strong binding affinity to the enzyme as well as altering the enzymic conformation.

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Kumar, Ritesh. "In-silico Studies on Phloroglucinol and SARS CoV2MPro." Bioscience Biotechnology Research Communications 14, no. 7 (July 25, 2021): 278–82. http://dx.doi.org/10.21786/bbrc/14.7.61.

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Franklin, Ronald. "In Silico Studies in ADME/Tox: Caveat Emptor." Current Computer Aided-Drug Design 5, no. 2 (June 1, 2009): 128–38. http://dx.doi.org/10.2174/157340909788451937.

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Petrov, Andrii Y., Paul D. Docherty, Mathieu Sellier, and J. Geoffrey Chase. "Multi-frequency Rayleigh damped elastography: in silico studies." Medical Engineering & Physics 37, no. 1 (January 2015): 55–67. http://dx.doi.org/10.1016/j.medengphy.2014.10.007.

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Li, Albert P., and Matthew Segall. "Early ADME/Tox studies and in silico screening." Drug Discovery Today 7, no. 1 (January 2002): 25–27. http://dx.doi.org/10.1016/s1359-6446(01)02117-1.

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Yurina, Valentina, and Oktavia Rahayu Adianingsih. "Predicting epitopes for vaccine development using bioinformatics tools." Therapeutic Advances in Vaccines and Immunotherapy 10 (January 2022): 251513552211002. http://dx.doi.org/10.1177/25151355221100218.

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Epitope-based DNA vaccine development is one application of bioinformatics or in silico studies, that is, computational methods, including mathematical, chemical, and biological approaches, which are widely used in drug development. Many in silico studies have been conducted to analyze the efficacy, safety, toxicity effects, and interactions of drugs. In the vaccine design process, in silico studies are performed to predict epitopes that could trigger T-cell and B-cell reactions that would produce both cellular and humoral immune responses. Immunoinformatics is the branch of bioinformatics used to study the relationship between immune responses and predicted epitopes. Progress in immunoinformatics has been rapid and has led to the development of a variety of tools that are used for the prediction of epitopes recognized by B cells or T cells as well as the antigenic responses. However, the in silico approach to vaccine design is still relatively new; thus, this review is aimed at increasing understanding of the importance of in silico studies in the design of vaccines and thereby facilitating future research in this field.

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Kano, Eunice, Chang Chiann, Kazuo Fukuda, and Valentina Porta. "Effect of Different Sampling Schedules on Results of Bioavailability and Bioequivalence Studies: Evaluation by Means of Monte Carlo Simulations." Drug Research 67, no. 08 (May 23, 2017): 451–57. http://dx.doi.org/10.1055/s-0043-105797.

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AbstractBioavailability and bioequivalence study is one of the most frequently performed investigations in clinical trials. Bioequivalence testing is based on the assumption that 2 drug products will be therapeutically equivalent when they are equivalent in the rate and extent to which the active drug ingredient or therapeutic moiety is absorbed and becomes available at the site of drug action. In recent years there has been a significant growth in published papers that use in silico studies based on mathematical simulations to analyze pharmacokinetic and pharmacodynamic properties of drugs, including bioavailability and bioequivalence aspects. The goal of this study is to evaluate the usefulness of in silico studies as a tool in the planning of bioequivalence, bioavailability and other pharmacokinetic assays, e.g., to determine an appropriate sampling schedule. Monte Carlo simulations were used to define adequate blood sampling schedules for a bioequivalence assay comparing 2 different formulations of cefadroxil oral suspensions. In silico bioequivalence studies comparing different formulation of cefadroxil oral suspensions using various sampling schedules were performed using models. An in vivo study was conducted to confirm in silico results. The results of in silico and in vivo bioequivalence studies demonstrated that schedules with fewer sampling times are as efficient as schedules with larger numbers of sampling times in the assessment of bioequivalence, but only if Tmax is included as a sampling time. It was also concluded that in silico studies are useful tools in the planning of bioequivalence, bioavailability and other pharmacokinetic in vivo assays.

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Santosh Kumar, Badampudi, Gudhi Madhu, and Lk Ravindranath. "Synthesis, antimicrobial evaluation and in silico studies of novel 3,4-disubstituted pyrrolidinesulfonamides." Chemical Bulletin of Kazakh National University, no. 4 (December 30, 2019): 28–40. http://dx.doi.org/10.15328/cb1044.

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3,4-Disubstituted pyrrolidinesulfonamides were synthesized and screened for their antimicrobial activity. Title compounds were established as potent antibacterial and antifungal agents. Noteworthy antimicrobial activity was found for the title compounds against the tested microorganisms. They exhibit comparable results with standard drugs. Besides the in vitro antimicrobial activity, the synthesized compounds were evaluated for their in silico inhibitory activity on active site of β-glucosidase enzyme. In silico studies were done by GOLD docking method against β-glucosidase 3VKK (PDB Id). In silico studies were conducted to evaluate the ability of synthesized compounds to inhibit the β-glucosidase enzyme. The results revealed that 3,4-disubstitutedpyrrolidinesulfonamides are the potent β-glucosidase inhibitors by binding at the active site. A sensible inhibition against β-glucosidases was observed for the compound with 13,4-oxadizole ring has higher β-glucosidase inhibition activity than the other compounds. The free energy of binding and inhibition constant (Ki) of the docked compounds were evaluated and presented.

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Suravajhala, Renuka, and Pritish Kumar Varadwaj. "STUDIES ON 8-TERTBUTYL CAFFEINE: AN IN SILICO APPROACH TO MECHANISTIC STUDIES." International Journal for Computational Biology 2, no. 1 (April 9, 2014): 12. http://dx.doi.org/10.34040/ijcb.2.1.2014.12.

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De, Baishakhi, Koushik Bhandari, Francisco J. B. Mendonça, Marcus T. Scotti, and Luciana Scotti. "Computational Studies in Drug Design Against Cancer." Anti-Cancer Agents in Medicinal Chemistry 19, no. 5 (June 27, 2019): 587–91. http://dx.doi.org/10.2174/1871520618666180911125700.

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Background: The application of in silico tools in the development of anti cancer drugs. Objective: The summing of different computer aided drug design approaches that have been applied in the development of anti cancer drugs. Methods: Structure based, ligand based, hybrid protein-ligand pharmacophore methods, Homology modeling, molecular docking aids in different steps of drug discovery pipeline with considerable saving in time and expenditure. In silico tools also find applications in the domain of cancer drug development. Results: Structure-based pharmacophore modeling aided in the identification of PUMA inhibitors, structure based approach with high throughput screening for the development of Bcl-2 inhibitors, to derive the most relevant protein-protein interactions, anti mitotic agents; I-Kappa-B Kinase β (IKK- β) inhibitor, screening of new class of aromatase inhibitors that can be important targets in cancer therapy. Conclusion: Application of computational methods in the design of anti cancer drugs was found to be effective.

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Scotti, Marcus Tullius, Alex France Messias Monteiro, Jéssika de Oliveira Viana, Francisco Jaime Bezerra Mendonça Junior, Hamilton M. Ishiki, Ernestine Nkwengoua Tchouboun, Rodrigo Santos A. De Araújo, and Luciana Scotti. "Recent Theoretical Studies Concerning Important Tropical Infections." Current Medicinal Chemistry 27, no. 5 (March 16, 2020): 795–834. http://dx.doi.org/10.2174/0929867326666190711121418.

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Neglected Tropical Diseases (NTDs) form a group of diseases that are strongly associated with poverty, flourish in impoverished environments, and thrive best in tropical areas, where they tend to present overlap. They comprise several diseases, and the symptoms vary dramatically from disease to disease, often causing from extreme pain, and untold misery that anchors populations to poverty, permanent disability, and death. They affect more than 1 billion people worldwide; mostly in poor populations living in tropical and subtropical climates. In this review, several complementary in silico approaches are presented; including identification of new therapeutic targets, novel mechanisms of activity, high-throughput screening of small-molecule libraries, as well as in silico quantitative structure-activity relationship and recent molecular docking studies. Current and active research against Sleeping Sickness, American trypanosomiasis, Leishmaniasis and Schistosomiasis infections will hopefully lead to safer, more effective, less costly and more widely available treatments against these parasitic forms of Neglected Tropical Diseases (NTDs) in the near future.

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Jan, Rifat, Meganathan Kannan, Tobias Obser, Md Imtaiyaz Hassan, Florian Oyen, Ulrich Budde, Renu Saxena, Firdos Ahmad, and Reinhard Schneppenheim. "Characterisation of mutations and molecular studies of type 2 von Willebrand disease." Thrombosis and Haemostasis 109, no. 01 (2013): 39–46. http://dx.doi.org/10.1160/th12-07-0475.

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SummaryType 2 von Willebrand disease (VWD) is characterised by qualitative defects in von Willebrand factor (VWF). Exon 28 of the VWF gene is known to be a hot spot for type 2 VWD mutations. The goal of this study was to characterise the mutations in VWF exon 28 and understand the molecular basis of phenotypes through in vitro and in silico studies. Mutation screening was performed in 56 type 2 VWD patients through direct sequencing. Expression vectors for five mutations were transiently expressed in 293-EBNA cells to understand the mutations pathology. Furthermore, in silico structure analysis was performed for 13 missense mutations.A total of 16 including eight novel mutations were detected in 23 (41%) patients. Of these, 15 were missense (including seven V1439M, A1464P, M1495L, I1509V, R1527Q, N1635I and A1647D novel ones) and one was a novel gene conversion. Expression studies and characterisation of recombinant VWF suggested the loss of VWF function for mutants P1266Q, V1439M and N1635I and gain of function for mutant R1308C. No apparent defect was seen in mutant N1231S. In silico structure analysis suggested the probable gain or loss of hydrogen/van der Waals interactions in 10 mutant proteins. In conclusion, type 2A mutations and gene conversion were found to be a common cause of type 2 VWD. Expression studies suggest the mutations N1635I for type 2A(II), P1266Q and V1439M for type 2M, R1308C for type 2B VWD and N1231S as a non-causative variant. Moreover, in silico studies of the mutants show the probable cause of respective phenotypes.

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Damayanti, Dini. "Potency Of Vigna Angularis Against Erα Through In Silico Studies." Jurnal Kesehatan Islam : Islamic Health Journal 9, no. 2 (September 24, 2020): 49. http://dx.doi.org/10.33474/jki.v9i2.8871.

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Vigna angularis, from the legume family, contains phytoestrogens. Phytoestrogens can activate estrogen receptors and are safer than estrogen. The study aims to analyze the potential of Vigna angularis as an activator of estrogen receptor-α (ERα) through in silico studies. The analysis of molecular docking used SAR (Structure Activity Relationship). A previous study has shown that Vigna angularis contains isoflavones such as Genestein (0.5%), daidzein (14.9%), glycitein (25.8%), formononetin (13%), and biochanin A (45.5%). The results of molecular docking to ERα show that genestein has a free energy binding value of -9.3 and the same amino acid structure, with a control level over estrogen of 66%. In conclusion, in silico studies have shown that genestein from Vigna angularis is the main component that activates the ERα.

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Muruganandam, L., and Maheswari R. "ANTI CANCER STUDIES OF SELECTIVE MANNICH BASES BY IN SILICO METHOD." International Journal of Current Pharmaceutical Research 10, no. 2 (March 15, 2018): 81. http://dx.doi.org/10.22159/ijcpr.2018v10i2.25877.

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Objective: To evaluate the anticancer activities of selective Mannich bases by in silico methods.Methods: X-ray crystallographic structure of Estrogen receptor protein (PDB ID 2YAT) was downloaded from the protein data bank (PDB) and is docked with the target Mannich bases using Accelyrs Discovery Studio client version 2.5 software.Results: Based on the in silico analysis results of the target compounds with standard drug tamoxifen, the best-docked compound is identified and its anticancer activity is confirmed by using in vitro MTS analysis using Raju and Jurkat cell lines.Conclusion: The mannich base compound N-[(Diphenylamino) methyl] acetamide showed fourfold higher activity than standard drug tamoxifen, may be used to overcome the drug resistance of Estrogen receptor protein.

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Ivashchenko, Dmitriy V., Anastasia V. Rudik, Andrey A. Poloznikov, Sergey V. Nikulin, Valeriy V. Smirnov, Alexander G. Tonevitsky, Eugeniy A. Bryun, and Dmitriy A. Sychev. "Which cytochrome P450 metabolizes phenazepam? Step by step in silico, in vitro, and in vivo studies." Drug Metabolism and Personalized Therapy 33, no. 2 (June 27, 2018): 65–73. http://dx.doi.org/10.1515/dmpt-2017-0036.

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Abstract Background: Phenazepam (bromdihydrochlorphenylbenzodiazepine) is the original Russian benzodiazepine tranquilizer belonging to 1,4-benzodiazepines. There is still limited knowledge about phenazepam’s metabolic liver pathways and other pharmacokinetic features. Methods: To determine phenazepam’s metabolic pathways, the study was divided into three stages: in silico modeling, in vitro experiment (cell culture study), and in vivo confirmation. In silico modeling was performed on the specialized software PASS and GUSAR to evaluate phenazepam molecule affinity to different cytochromes. The in vitro study was performed using a hepatocytes’ cell culture, cultivated in a microbioreactor to produce cytochrome P450 isoenzymes. The culture medium contained specific cytochrome P450 isoforms inhibitors and substrates (for CYP2C9, CYP3A4, CYP2C19, and CYP2B6) to determine the cytochrome that was responsible for phenazepam’s metabolism. We also measured CYP3A activity using the 6-betahydroxycortisol/cortisol ratio in patients. Results: According to in silico and in vitro analysis results, the most probable metabolizer of phenazepam is CYP3A4. By the in vivo study results, CYP3A activity decreased sufficiently (from 3.8 [95% CI: 2.94–4.65] to 2.79 [95% CI: 2.02–3.55], p=0.017) between the start and finish of treatment in patients who were prescribed just phenazepam. Conclusions: Experimental in silico and in vivo studies confirmed that the original Russian benzodiazepine phenazepam was the substrate of CYP3A4 isoenzyme.

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Szymanski, Sebastian, and Irena Majerz. "In Silico Studies on Sennidines—Natural Dianthrones from Senna." Biology 10, no. 6 (May 26, 2021): 468. http://dx.doi.org/10.3390/biology10060468.

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The rapid development of technology allows for more accurate research of biological systems with the use of in silico methods. One of the tools is the quantum-chemical method used for determining the structure, properties and interactions of molecules of great pharmacological importance. The accuracy of theoretical models is increasing and can be a real help in biology, chemistry and pharmacy. The aim of the study is to determine the spatial structure and intramolecular interactions of sennidines—natural pharmaceutical substances present in Senna species. Calculations carried out in the gas-phase and in the solvent model, compared with the available experimental data indicate the possibility of sennidines to form conformers. QTAIM and NCI analysis suggests the presence of many intramolecular interactions in the sennidin structure. Taking into account the lowest energy optimized structure, it can be predicted that the sennidin in the gauche conformation will be present in the plant material. The single C-C bond connecting the anthrone moieties is elongated and its reduced Bond Dissociation Energy (BDE) could be the cause of an easy breakdown of the sennidin molecule into monoanthrones. This work contains data on theoretical, vibrational and electron excitation spectra, which can be used in the analysis of experimental samples.

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Makhouri, Farahnaz Rezaei, and Jahan B. Ghasemi. "In Silico Studies in Drug Research Against Neurodegenerative Diseases." Current Neuropharmacology 16, no. 6 (June 8, 2018): 664–725. http://dx.doi.org/10.2174/1570159x15666170823095628.

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Scheidel, Jennifer, Leonie Amstein, Jörg Ackermann, Ivan Dikic, and Ina Koch. "In Silico Knockout Studies of Xenophagic Capturing of Salmonella." PLOS Computational Biology 12, no. 12 (December 1, 2016): e1005200. http://dx.doi.org/10.1371/journal.pcbi.1005200.

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Rinanda, T. "In Silico Studies in Antimicrobial Peptides Design and Development." IOP Conference Series: Earth and Environmental Science 305 (July 25, 2019): 012062. http://dx.doi.org/10.1088/1755-1315/305/1/012062.

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Ahmad Pasha, Farhan, Muhammad Muddassar, Anil Kumar Srivastava, and Seung Joo Cho. "In silico QSAR studies of anilinoquinolines as EGFR inhibitors." Journal of Molecular Modeling 16, no. 2 (July 10, 2009): 263–77. http://dx.doi.org/10.1007/s00894-009-0534-x.

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Chatterjee, Subhasish, and Katherine Liu. "In Silico Structural Studies of a Tripeptide Building Block." Biophysical Journal 114, no. 3 (February 2018): 184a. http://dx.doi.org/10.1016/j.bpj.2017.11.1028.

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Ansari, Bushra, Haroon Khan, Muhammad Saeed Jan, Khalaf F. Alsharif, Khalid J. Alzahrani, Umer Rashid, and Abdul Saboor Pirzada. "Synthesis, Characterization, and Pharmacokinetic Studies of Thiazolidine-2,4-Dione Derivatives." Journal of Chemistry 2023 (January 16, 2023): 1–11. http://dx.doi.org/10.1155/2023/9462176.

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Various derivatives of thiazolidine-2,4-dione (C1–C5) were designed and synthesized by chemical reaction with 4-nitrobenzaldehyde using Knoevenagel reaction conditions which results in the reduction of nitro group to amine and further modification results in target compounds. The chemical structures of all the 2,4-thiazolidinedione derivatives have been elucidated by 1H and 13C NMR spectroscopy. These compounds were further characterized by in silico ADME (absorption, distribution, metabolism, and excretion) studies. The pharmacokinetic properties were assessed by SwissADME software. The in silico ADME (absorption, distribution, metabolism, and excretion) assessment reveals that all derivatives (C1 to C5) have 5 to 7 rotatable bonds. Lipophilicity and water solubility showed that C1, C2, and C4 are water soluble except for C3 and C5 which are moderately soluble. All the compounds have high GI absorption except C3. None of the derivatives are blood-brain barrier permeant. Drug metabolism of TZDs derivatives showed that C3 was identified as an inhibitor of CYP2C9 and C5 as an inhibitor of CYP1A2 and CYP2C19. Drug likeness properties indicate that C1 has only one violation of the Ghose rule while C3 has violations in the Ghose and Egan rules. The in silico pharmacokinetic studies revealed high GI absorption and the inability to pass blood-brain barrier which can be further assessed by in vitro and in vivo antihyperglycemic activity. This study will contribute to providing TZDs derivatives with an improved pharmacokinetic profile and decreased toxicity.

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Zhou, Yang, Guanglin Kuang, Junhao Li, Christer Halldin, Agneta Nordberg, Bengt Långström, Yaoquan Tu, and Hans Ågren. "In silico studies of ASEM analogues targeting α7-nAChR and experimental verification." RSC Advances 11, no. 7 (2021): 3942–51. http://dx.doi.org/10.1039/d0ra10435c.

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Kovar, Lukas, Lena Wien, Dominik Selzer, Yvonne Kohl, Robert Bals, and Thorsten Lehr. "In Vitro–In Silico Modeling of Caffeine and Diclofenac Permeation in Static and Fluidic Systems with a 16HBE Lung Cell Barrier." Pharmaceuticals 15, no. 2 (February 18, 2022): 250. http://dx.doi.org/10.3390/ph15020250.

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Static in vitro permeation experiments are commonly used to gain insights into the permeation properties of drug substances but exhibit limitations due to missing physiologic cell stimuli. Thus, fluidic systems integrating stimuli, such as physicochemical fluxes, have been developed. However, as fluidic in vitro studies display higher complexity compared to static systems, analysis of experimental readouts is challenging. Here, the integration of in silico tools holds the potential to evaluate fluidic experiments and to investigate specific simulation scenarios. This study aimed to develop in silico models that describe and predict the permeation and disposition of two model substances in a static and fluidic in vitro system. For this, in vitro permeation studies with a 16HBE cellular barrier under both static and fluidic conditions were performed over 72 h. In silico models were implemented and employed to describe and predict concentration–time profiles of caffeine and diclofenac in various experimental setups. For both substances, in silico modeling identified reduced apparent permeabilities in the fluidic compared to the static cellular setting. The developed in vitro–in silico modeling framework can be expanded further, integrating additional cell tissues in the fluidic system, and can be employed in future studies to model pharmacokinetic and pharmacodynamic drug behavior.

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Achuthanandhan, Jyothi, and Baskar Lakshmanan. "Docking studies of tetra substituted pyrazolone derivatives as potential antiviral agents." JOURNAL OF PHARMACEUTICAL CHEMISTRY 5, no. 2 (December 20, 2018): 5–8. http://dx.doi.org/10.14805/jphchem.2018.art103.

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In an attempt to find potential antiviral agents, a series of pyrazolones (PA1-PA6& PC1-PC6) were designed and evaluated for their DENVNS5 (RNA-dependent RNA polymerase) inhibitory activity. Molecular docking studies of all the designed compounds into the binding site of DENVNS5 (PDB Code: 4C11) were performed to gain a comprehensive understanding into rational binding modes. These compounds were also screened for in silico drug-likeliness properties on the basis of the absorption, distribution, metabolism and excretion (ADME) prediction. Among all the synthesized compounds, analogue PA6showed superior inhibitory activity against RNA dependent RNA polymerase. SAR study indicated that the presence of an electron withdrawing substitution on pyrazolone derivatives significantly improves its binding interaction with the protein.Results of ADME prediction revealed that most of these compounds showed in silico drug-likeliness.

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Assirey, Eman, Azhaar Alsaggaf, Arshi Naqvi, Ziad Moussa, Rawda M. Okasha, Tarek H. Afifi, and Alaa S. Abd-El-Aziz. "Synthesis, Biological Assessment, and Structure Activity Relationship Studies of New Flavanones Embodying Chromene Moieties." Molecules 25, no. 3 (January 27, 2020): 544. http://dx.doi.org/10.3390/molecules25030544.

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Novel flavanones that incorporate chromene motifs are synthesized via a one-step multicomponent reaction. The structures of the new chromenes are elucidated by using IR, 1H-NMR, 13C-NMR, 1H-1H COSY, HSQC, HMBC, and elemental analysis. The new compounds are screened for their in vitro antimicrobial and cytotoxic activities. The antimicrobial properties are investigated and established against seven human pathogens, employing the agar well diffusion method and the minimum inhibitory concentrations. A majority of the assessed derivatives are found to exhibit significant antimicrobial activities against most bacterial strains, in comparison to standard reference drugs. Moreover, their cytotoxicity is appraised against four different human carcinoma cell lines: human colon carcinoma (HCT-116), human hepatocellular carcinoma (HepG-2), human breast adenocarcinoma (MCF-7), and adenocarcinoma human alveolar basal epithelial cell (A-549). All the desired compounds are subjected to in-silico studies, forecasting their drug likeness, bioactivity, and the absorption, distribution, metabolism, and excretion (ADME) properties prior to their synthetic assembly. The in-silico molecular docking evaluation of all the targeted derivatives is undertaken on gyrase B and the cyclin-dependent kinase. The in-silico predicted outcomes were endorsed by the in vitro studies.

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Verma, Sonia, Akashdeep Singh Pathania, Somesh Baranwal, and Pradeep Kumar. "Synthesis and In silico Studies of Quinazolinone Derivatives as PARP-1 Inhibitors." Letters in Drug Design & Discovery 17, no. 12 (November 19, 2020): 1552–65. http://dx.doi.org/10.2174/1570180817999200719152959.

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Background: Cancer is a leading cause of deaths worldwide, accounting for 9.6 million deaths in 2018. According to the WHO, the most common causes of cancer deaths are lung, colorectal, stomach liver and breast cancer. Introduction: PARP-1 has a crucial role in cell proliferation, survival and death due to its role in the regulation of multiple biological processes. Quinazolinone and its derivatives represent a large class of biologically active compounds that exhibit a broad spectrum of biological activities such as anti-HIV, anticancer, antifungal, antibacterial, anticonvulsant, anti-inflammatory, antidepressant, antimalarial, antioxidant and antileishmanial activities. Methods: In this study, we have synthesized quinazolinone derivatives by reaction of 2- aminobenzamide and substituted benzaldehydes. The synthesized compounds were also screened in silico for their PARP-1 binding affinities by molecular docking studies using Schrodinger 2016 software. In silico ADME studies were also performed for the synthesized compounds by using QikProp tool of Schrodinger software. Results: Results of in silico studies indicated that quinazolinone derivatives exhibited a good affinity towards the active site of PARP-1. Out of all synthesized compounds, SVA-11 exhibited a maximum dock score (-10.421). Results of ADME studies indicated the suitability of synthesized compounds as drug candidates. Conclusion: The synthesized compounds showed better docking scores than reference drug valiparib. Furthermore, they exhibited favorable ADME profile. Therefore, they may serve as lead compounds in the discovery of PARP-1 inhibitors.

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Fröhlich, Eleonore. "Replacement Strategies for Animal Studies in Inhalation Testing." Sci 3, no. 4 (December 1, 2021): 45. http://dx.doi.org/10.3390/sci3040045.

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Animal testing is mandatory in drug testing and is the gold standard for toxicity and efficacy evaluations. This situation is expected to change in the future as the 3Rs principle, which stands for the replacement, reduction, and refinement of the use of animals in science, is reinforced by many countries. On the other hand, technologies for alternatives to animal testing have increased. The need to develop and use alternatives depends on the complexity of the research topic and also on the extent to which the currently used animal models can mimic human physiology and/or exposure. The lung morphology and physiology of commonly used animal species differs from that of human lungs, and the realistic inhalation exposure of animals is challenging. In vitro and in silico methods can assess important aspects of the in vivo effects, namely particle deposition, dissolution, action at, and permeation through, the respiratory barrier, and pharmacokinetics. This review discusses the limitations of animal models and exposure systems and proposes in vitro and in silico techniques that could, when used together, reduce or even replace animal testing in inhalation testing in the future.

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Heller, A. A., S. Y. Lockwood, T. M. Janes, and D. M. Spence. "Technologies for Measuring Pharmacokinetic Profiles." Annual Review of Analytical Chemistry 11, no. 1 (June 12, 2018): 79–100. http://dx.doi.org/10.1146/annurev-anchem-061417-125611.

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The creation of a pharmacokinetic (PK) curve, which follows the plasma concentration of an administered drug as a function of time, is a critical aspect of the drug development process and includes such information as the drug's bioavailability, clearance, and elimination half-life. Prior to a drug of interest gaining clearance for use in human clinical trials, research is performed during the preclinical stages to establish drug safety and dosing metrics from data obtained from the PK studies. Both in vivo animal models and in vitro platforms have limitations in predicting human reaction to a drug due to differences in species and associated simplifications, respectively. As a result, in silico experiments using computer simulation have been implemented to accurately predict PK parameters in human studies. This review assesses these three approaches (in vitro, in vivo, and in silico) when establishing PK parameters and evaluates the potential for in silico studies to be the future gold standard of PK preclinical studies.

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Journal articles on the topic 'SILICO STUDIES'

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