In silico design, synthesis and antitubercular activity of novel 2-acylhydrazono-5-arylmethylene-4-thiazolidinones as enoyl-acyl carrier protein reductase inhibitors

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dc.authorwosidDingiş Birgül, Serap İpek/AAY-9924-2021
dc.contributor.authorBirgul, Serap Ipek Dingis
dc.contributor.authorKumari, Jyothi
dc.contributor.authorTamhaev, Rasoul
dc.contributor.authorMourey, Lionel
dc.contributor.authorLherbet, Christian
dc.contributor.authorSriram, Dharmarajan
dc.contributor.authorAkdemir, Atilla
dc.date.accessioned2024-05-19T14:45:55Z
dc.date.available2024-05-19T14:45:55Z
dc.date.issued2024
dc.departmentİstinye Üniversitesien_US
dc.description.abstractMycobacteria regulate the synthesis of mycolic acid through the fatty acid synthase system type 1 (FAS I) and the fatty acid synthase system type-2 (FAS-II). Because mammalian cells exclusively utilize the FAS-I enzyme system for fatty acid production, targeting the FAS-II enzyme system could serve as a specific approach for developing selective antimycobacterial drugs. Enoyl-acyl carrier protein reductase enzyme (MtInhA), part of the FAS-II enzyme system, contains the NADH cofactor in its active site and reduces the intermediate. Molecular docking studies were performed on an in-house database (similar to 2200 compounds). For this study, five different crystal structures of MtInhA (PDB Code: 4TZK, 4BQP, 4D0S, 4BGE, 4BII) were used due to rotamer difference, mutation and the presence of cofactors. Molecular dynamics simulations (250 ns) were performed for the novel 2-acylhydrazono-5-arylmethylene-4-thiazolidinones derivatives selected by molecular docking studies. Twenty-three compounds selected by in silico methods were synthesized. Antitubercular activity and MtInhA enzyme inhibition studies were performed for compounds whose structures were elucidated by IR,H-1-NMR,C-13-NMR, HSQC, HMBC, MS and elemental analysis. Communicated by Ramaswamy H. Sarmaen_US
dc.description.sponsorshipCouncil of Higher Education; Scientific and Technological Research Council of Turkey [TUBIdot;TAK-BIdot;DEB-2211-A]; [CoHE-YOK100/2000]en_US
dc.description.sponsorshipSerap & Idot;pek Dingi & scedil; Birguel was supported with scholarships by the Council of Higher Education (CoHE-YOK100/2000) and The Scientific and Technological Research Council of Turkey (TUB & Idot;TAK-B & Idot;DEB-2211-A). Figures 4, 5 and 8 presented in the supplemental material of this article have been partially reproduced from Trawally et al. (2023) (Figures S73, S74 and S75), Copyright (2023), with permission from Elsevier (Licence number: 5730950160537).en_US
dc.identifier.doi10.1080/07391102.2024.2319678
dc.identifier.issn0739-1102
dc.identifier.issn1538-0254
dc.identifier.pmid38450660en_US
dc.identifier.scopus2-s2.0-85187149727en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.urihttps://doi.org10.1080/07391102.2024.2319678
dc.identifier.urihttps://hdl.handle.net/20.500.12713/5391
dc.identifier.wosWOS:001180288000001en_US
dc.identifier.wosqualityN/Aen_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.language.isoenen_US
dc.publisherTaylor & Francis Incen_US
dc.relation.ispartofJournal of Biomolecular Structure & Dynamicsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.snmz20240519_kaen_US
dc.subjectMycobacterium Tuberculosisen_US
dc.subjectMtinha Inhibitorsen_US
dc.subjectThiazolidin-4-Oneen_US
dc.subjectMolecular Modelingen_US
dc.subjectMolecular Dynamicsen_US
dc.titleIn silico design, synthesis and antitubercular activity of novel 2-acylhydrazono-5-arylmethylene-4-thiazolidinones as enoyl-acyl carrier protein reductase inhibitorsen_US
dc.typeArticleen_US

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