<i>in Silico</I> Design, Synthesis and Antitubercular Activity of Novel 2-Acylhydrazono as Enoyl-Acyl Carrier Protein Reductase Inhibitors

dc.authorscopusid 57218545718
dc.authorscopusid 58059893100
dc.authorscopusid 57947321100
dc.authorscopusid 6701410917
dc.authorscopusid 6602628524
dc.authorscopusid 7005623982
dc.authorscopusid 8912960500
dc.authorwosid kucukguzel, ilkay/Z-1541-2019
dc.authorwosid Dingiş Birgül, Serap İpek/AAY-9924-2021
dc.authorwosid Lherbet, Christian/O-4408-2017
dc.authorwosid Akdemir, Atilla/G-2595-2015
dc.contributor.author Küçükgüzel, İlkay
dc.contributor.author Kumari, Jyothi
dc.contributor.author Tamhaev, Rasoul
dc.contributor.author Mourey, Lionel
dc.contributor.author Lherbet, Christian
dc.contributor.author Sriram, Dharmarajan
dc.contributor.author Kucukguzel, Ilkay
dc.contributor.other Eczacılık Meslek Bilimleri Bölümü
dc.date.accessioned 2025-01-11T13:03:14Z
dc.date.available 2025-01-11T13:03:14Z
dc.date.issued 2024
dc.department Fenerbahçe University en_US
dc.department-temp [Birgul, Serap Ipek Dingis; Kucukguzel, Ilkay] Marmara Univ, Inst Hlth Sci, Dept Pharmaceut Chem, Istanbul, Turkiye; [Birgul, Serap Ipek Dingis] Bezmialem Vakif Univ, Dept Pharmacol, Comp Aided Drug Discovery Lab, Istanbul, Turkiye; [Kumari, Jyothi; Sriram, Dharmarajan] Birla Inst Technol & Sci Pilani, Dept Pharm, Hyderabad Campus, Hyderabad, India; [Tamhaev, Rasoul; Lherbet, Christian] Univ Toulouse 3 Paul Sabatier, Lab Synth & Phys Chim Mol Interet Biol, Toulouse, France; [Tamhaev, Rasoul; Mourey, Lionel] Univ Toulouse, Inst Pharmacol & Biol Struct IPBS, CNRS, UPS, Toulouse, France; [Akdemir, Atilla] Istinye Univ, Fac Pharm, Dept Pharmacol, Istanbul, Turkiye; [Kucukguzel, Ilkay] Fenerbahce Univ, Fac Pharm, Dept Pharmaceut Chem, Istanbul, Turkiye en_US
dc.description.abstract Mycobacteria 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. Sarma en_US
dc.description.sponsorship Council of Higher Education; Scientific and Technological Research Council of Turkey [TUBIdot;TAK-BIdot;DEB-2211-A]; [CoHE-YOK100/2000] en_US
dc.description.sponsorship Serap & 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.description.woscitationindex Science Citation Index Expanded
dc.identifier.citation 1
dc.identifier.doi 10.1080/07391102.2024.2319678
dc.identifier.issn 0739-1102
dc.identifier.issn 1538-0254
dc.identifier.pmid 38450660
dc.identifier.scopus 2-s2.0-85187149727
dc.identifier.scopusquality Q1
dc.identifier.uri https://doi.org/10.1080/07391102.2024.2319678
dc.identifier.uri https://hdl.handle.net/20.500.14627/243
dc.identifier.wos WOS:001180288000001
dc.identifier.wosquality Q1
dc.language.iso en en_US
dc.publisher Taylor & Francis inc en_US
dc.relation.publicationcategory Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı en_US
dc.rights info:eu-repo/semantics/openAccess en_US
dc.scopus.citedbyCount 5
dc.subject Mycobacterium Tuberculosis en_US
dc.subject Mtinha Inhibitors en_US
dc.subject Thiazolidin-4-One en_US
dc.subject Molecular Modeling en_US
dc.subject Molecular Dynamics en_US
dc.title <i>in Silico</I> Design, Synthesis and Antitubercular Activity of Novel 2-Acylhydrazono as Enoyl-Acyl Carrier Protein Reductase Inhibitors en_US
dc.type Article en_US
dc.wos.citedbyCount 4
dspace.entity.type Publication
relation.isAuthorOfPublication 39fe9358-c29b-4ad5-a5e1-597b038fbe7f
relation.isAuthorOfPublication.latestForDiscovery 39fe9358-c29b-4ad5-a5e1-597b038fbe7f
relation.isOrgUnitOfPublication 5052e089-e75d-4aec-a280-6353973e4819
relation.isOrgUnitOfPublication.latestForDiscovery 5052e089-e75d-4aec-a280-6353973e4819

Files