Novel Dibenzoazepine-Substituted Triazole Hybrids as Cholinesterase and Carbonic Anhydrase Inhibitors and Anticancer Agents: Synthesis, Characterization, Biological Evaluation, and In Silico Studies

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dc.authoridOnder, Alper/0000-0002-0775-0053
dc.authoridComert Onder, Ferah/0000-0002-4037-1979
dc.contributor.authorErdogan, Musa
dc.contributor.authorOnder, Alper
dc.contributor.authorDemir, Yeliz
dc.contributor.authorComert Onder, Ferah
dc.date.accessioned2025-01-27T21:01:37Z
dc.date.available2025-01-27T21:01:37Z
dc.date.issued2024
dc.departmentÇanakkale Onsekiz Mart Üniversitesi
dc.description.abstractThe new dibenzoazepine-substituted triazole hybrids (12-20) were designed by molecular hybridization approach and synthesized utilizing the Cu(I)-catalyzed click reaction. The hybrid structures (12-20) were obtained in high yields (74-98%) with a simple two-step synthesis strategy and fully characterized. These compounds were assessed for their influence on various metabolic enzymes including human carbonic anhydrase isoenzymes (hCA I and hCA II), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE). The Ki values for the compounds concerning hCA I, hCA II, AChE, and BChE enzymes were in the ranges 29.94-121.69, 17.72-89.42, 14.09-44.68, and 1.15-48.82 nM, respectively. Compound 13 was 49.70-fold more active than tacrine (standard drug) for BChE and 5.49-fold for AChE. Compound 14 was 4.16-fold more active than acetazolamide (standard drug) for hCA I and 5.79-fold for hCA II. The cytotoxic effects of the synthesized click products were investigated on human triple-negative breast cancer cell lines. The IC50 values of the most effective compounds were calculated between 12.51 +/- 1.92 and 18.07 +/- 2.14 mu M in MDA-MB-231 and BT-549 cells. Molecular docking and ADME predictions were performed. Then, in vitro effective compounds were analyzed by molecular dynamics (MD) simulation and MM/GBSA calculation. Consequently, click products showed good cytotoxicity and inhibition potential on colony formation in cancer cells.
dc.description.sponsorshipKafkas ?niversitesi [2022-FM-41]; Research Foundation of Kafkas University; Canakkale Onsekiz Mart University Experimental Research Application and Research Center
dc.description.sponsorshipThe authors are grateful to the Research Foundation of Kafkas University for financial support under project 2022-FM-41, and Canakkale Onsekiz Mart University Experimental Research Application and Research Center (COMUDAM) for laboratory facilities.
dc.identifier.doi10.1021/acsomega.4c05804
dc.identifier.endpage46878
dc.identifier.issn2470-1343
dc.identifier.issue47
dc.identifier.pmid39619510
dc.identifier.scopus2-s2.0-85209240567
dc.identifier.scopusqualityQ1
dc.identifier.startpage46860
dc.identifier.urihttps://doi.org/10.1021/acsomega.4c05804
dc.identifier.urihttps://hdl.handle.net/20.500.12428/27124
dc.identifier.volume9
dc.identifier.wosWOS:001356516200001
dc.identifier.wosqualityN/A
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherAmer Chemical Soc
dc.relation.ispartofAcs Omega
dc.relation.publicationcategoryinfo:eu-repo/semantics/openAccess
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WoS_20250125
dc.subjectTacrine-Coumarin Hybrids
dc.subjectMolecular Docking
dc.subjectAcetylcholinesterase
dc.subjectAntioxidant
dc.subjectDesign
dc.subjectVitro
dc.titleNovel Dibenzoazepine-Substituted Triazole Hybrids as Cholinesterase and Carbonic Anhydrase Inhibitors and Anticancer Agents: Synthesis, Characterization, Biological Evaluation, and In Silico Studies
dc.typeArticle

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