Linking azoles to isoniazid via hydrazone bridge: Synthesis, crystal structure determination, antitubercular evaluation and computational studies

Basit Öğe Kaydı
dc.authoridArmakovic, Stevan/0000-0002-8049-9969
dc.authoridVagolu, Siva Krishna/0000-0003-1540-9995
dc.authoridGunduz, Miyase Gozde/0000-0002-2287-9509
dc.authoridArmakovic, Sanja/0000-0002-3665-1046
dc.authoridTonjum, Tone/0000-0002-1709-6921
dc.contributor.authorAslan, Ebru Kocak
dc.contributor.authorKrishna, Vagolu Siva
dc.contributor.authorArmakovic, Sanja J.
dc.contributor.authorArmakovic, Stevan
dc.contributor.authorSahin, Onur
dc.contributor.authorTonjum, Tone
dc.contributor.authorGunduz, Miyase Gozde
dc.date.accessioned2025-03-23T19:40:51Z
dc.date.available2025-03-23T19:40:51Z
dc.date.issued2022
dc.departmentSinop Üniversitesi
dc.description.abstractThe current emergence of drug-resistant and multidrug-resistant (MDR) Mycobacterium tuberculosis (Mtb) strains has complicated and hampered attempts to eliminate or considerably reduce the global prevalence of the often life-threatening disease tuberculosis (TB). Hence, the development of novel antitubercular agents is crucial to combat this challenge. Here, we applied the molecular hybridization approach to link isoniazid (INH), the frontline antitubercular drug, to various azole rings (pyrazole, imidazole, and triazole) through hydrazone functionality. The designed compounds were synthesized and characterized by using spectral techniques including IR, H-1 NMR, C-13 NMR and HRMS. Additionally, single crystal X-ray analysis was employed to resolve the proposed chemical structure of INH-T. All compounds were then extensively screened for their antitubercular activities against Mtb H37Rv, drug-resistant and MDR Mtb strains, as well as against a clinical Mtb isolate with no mutation. Notably, INH-azole hybrids presented outstanding antimycobacterial activity with negligible cytotoxicity. Computational methods based on density functional theory calculations and molecular dynamics simulations were applied to identify the characteristic reactive centers of the title compounds, predict stability towards autoxidation, understand their interactions with water molecules and predict the temperature dependence of density. Finally, molecular docking studies revealed that new INH-azole hybrids are likely to exert their antimycobacterial activity via direct inhibition of the Mtb InhA enzyme. (C) 2022 Elsevier B.V. All rights reserved.
dc.description.sponsorshipBAGEP Award of the Science Academy; Ministry of Education, Science and Technological Development of the Republic of Serbia [451-03-68/202214/200125]
dc.description.sponsorshipMGG acknowledges the financial support provided by the BAGEP Award of the Science Academy. MGG is also grateful to Prof. Dr. Gerhard Wolber, Freie Universitat Berlin-Germany, for providing the license of LigandScout 4.4. The authors would like to thank Scientific and Technological Research Application and Research Center, Sinop University, Turkey, for the use of the Bruker D8 QUEST diffractometer. SJA and SA acknowledge the financial support of the Ministry of Education, Science and Technological Development of the Republic of Serbia (Grant No. 451-03-68/202214/200125)
dc.identifier.doi10.1016/j.molliq.2022.118873
dc.identifier.issn0167-7322
dc.identifier.issn1873-3166
dc.identifier.scopus2-s2.0-85126390732
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1016/j.molliq.2022.118873
dc.identifier.urihttps://hdl.handle.net/11486/6434
dc.identifier.volume354
dc.identifier.wosWOS:000820288600004
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.language.isoen
dc.publisherElsevier
dc.relation.ispartofJournal of Molecular Liquids
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WOS_20250323
dc.subjectTuberculosis
dc.subjectMolecular hybridization
dc.subjectX-ray analysis
dc.subjectDFT
dc.subjectMolecular dynamics
dc.subjectInteractions with water
dc.titleLinking azoles to isoniazid via hydrazone bridge: Synthesis, crystal structure determination, antitubercular evaluation and computational studies
dc.typeArticle

Dosyalar

Koleksiyon

WoS İndeksli Yayınlar Koleksiyonu
Scopus İndeksli Yayınlar Koleksiyonu