Discovery of hydrazone containing thiadiazoles as Mycobacterium tuberculosis growth and enoyl acyl carrier protein reductase (InhA) inhibitors

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dc.authoridLherbet, Christian/0000-0001-5427-5040
dc.authoridGunduz, Miyase Gozde/0000-0002-2287-9509
dc.authoridVagolu, Siva Krishna/0000-0003-1540-9995
dc.contributor.authorDogan, Hilal
dc.contributor.authorDogan, Sengul Dilem
dc.contributor.authorGunduz, Miyase Gozde
dc.contributor.authorKrishna, Vagolu Siva
dc.contributor.authorLherbet, Christian
dc.contributor.authorSriram, Dharmarajan
dc.contributor.authorSahin, Onur
dc.date.accessioned2025-03-23T19:41:45Z
dc.date.available2025-03-23T19:41:45Z
dc.date.issued2020
dc.departmentSinop Üniversitesi
dc.description.abstractTuberculosis, caused by Mycobacterium tuberculosis, is a serious infectious disease and remains a global health problem. There is an increasing need for the discovery of novel therapeutic agents for its treatment due to the emerging multi-drug resistance. Herein, we present the rational design and the synthesis of eighteen new thiadiazolylhidrazones (TDHs) which were synthesized by intramolecular oxidative N-S bond formation reaction of 2-benzylidene-N-(phenylcarbamothioyl)hydrazine-lcarboximidamide derivatives by phenyliodine(III) bis(trifluoroacetate) (PIFA) under mild conditions. The compounds were characterized by various spectral techniques including FTIR, H-1 NMR, C-13 NMR and HRMS. Furthermore, the proposed structure of TDH12 was resolved by single-crystal X-ray analysis. The compounds were evaluated for their in vitro antitubercular activity against M. tuberculosis H37Rv. Among them, some compounds exhibited remarkable antimycobacterial activity, MIC = 0.78-6.25 mu g/mL, with low cytotoxicity. Additionally, the most active compounds were screened for their biological activities against M. tuberculosis in the nutrient starvation model. Enzyme inhibition assays and molecular docking studies revealed enoyl acyl carrier protein reductase (InhA) as the possible target enzyme of the compounds to show their antitubercular activities. (C) 2020 Elsevier Masson SAS. All rights reserved.
dc.description.sponsorshipResearch Foundation of Erciyes University [FYL-2019-9164]; Faculty of Pharmacy at Erciyes University
dc.description.sponsorshipThe authors are indebted to the Research Foundation of Erciyes University (Grant No: FYL-2019-9164) and the Faculty of Pharmacy at Erciyes University for their financial support of this work. The authors acknowledge to Scientific and Technological Research Application and Research Center, Sinop University, Turkey, for the use of the Bruker D8 QUEST diffractometer. M.G.G. would like to thank Prof. Dr. Gerhard Wolber, Freie Universitat Berlin, for providing the license for LigandScout 4.2.
dc.identifier.doi10.1016/j.ejmech.2020.112035
dc.identifier.issn0223-5234
dc.identifier.issn1768-3254
dc.identifier.pmid31951850
dc.identifier.scopus2-s2.0-85077745898
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1016/j.ejmech.2020.112035
dc.identifier.urihttps://hdl.handle.net/11486/6635
dc.identifier.volume188
dc.identifier.wosWOS:000515428100043
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherElsevier France-Editions Scientifiques Medicales Elsevier
dc.relation.ispartofEuropean Journal of Medicinal Chemistry
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WOS_20250323
dc.subjectSynthesis
dc.subjectThiadiazole
dc.subjectHydrazone
dc.subjectTuberculosis
dc.subjectInhA
dc.subjectMolecular modeling
dc.titleDiscovery of hydrazone containing thiadiazoles as Mycobacterium tuberculosis growth and enoyl acyl carrier protein reductase (InhA) inhibitors
dc.typeArticle

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