Synthesis and Molecular Docking of New N-Acyl Hydrazones-Benzimidazole as hCA I and II Inhibitors

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dc.authoridcelik, ismail/0000-0002-8146-1663
dc.authoridISIK, Aysen/0000-0002-1280-0019
dc.authoridKucukoglu, Kaan/0000-0001-8977-9775
dc.contributor.authorKucukoglu, Kaan
dc.contributor.authorCevik, Ulviye Acar
dc.contributor.authorNadaroglu, Hayrunnisa
dc.contributor.authorCelik, Ismail
dc.contributor.authorIsik, Aysen
dc.contributor.authorBostanci, Hayrani Eren
dc.contributor.authorOzkay, Yusuf
dc.date.accessioned2024-10-26T18:11:04Z
dc.date.available2024-10-26T18:11:04Z
dc.date.issued2023
dc.departmentSivas Cumhuriyet Üniversitesi
dc.description.abstractBackground The carbonic anhydrases (CAs) which are found in most living organisms is a member of the zinc-containing metalloenzyme family. The abnormal levels and activities are frequently associated with various diseases therefore CAs have become an attractive target for the design of inhibitors or activators that can be used in the treatment of those diseases. Methods Herein, we have designed and synthesized new benzimidazole-hydrazone derivatives to investigate the effects of these synthesized compounds on CA isoenzymes. Chemical structures of synthesized compounds were confirmed by H-1 NMR, C-13 NMR, and HRMS. The synthetic derivatives were screened for their inhibitory potential against carbonic anhydrase I and II by in vitro assay. Results These compounds have IC50 values of 5.156-1.684 mu M (hCA I) and 4.334-2.188 mu M (hCA II). Inhibition types and Ki values of the compounds were determined. The Ki values of the compounds were 5.44 +/- 0.14 mu M-0.299 +/- 0.01 mu M (hCA I) and 3.699 +/- 0.041 mu M-1.507 +/- 0.01 mu M (hCA II). The synthetic compounds displayed inhibitory action comparable to that of the clinically utilized reference substance, acetazolamide. According to this, compound 3p was the most effective molecule with an IC50 value of 1.684 mu M. Accordingly, the type of inhibition was noncompetitive and the Ki value was 0.299 +/- 0.01 mu M. Conclusion According to the in vitro test results, detailed protein-ligand interactions of the compound 3p, which is more active against hCA I than standard azithromycin (AZM), were analyzed. In addition, the cytotoxic effects of the compounds on the L929 healthy cell line were evaluated.
dc.identifier.doi10.2174/1573406419666221222143530
dc.identifier.endpage494
dc.identifier.issn1573-4064
dc.identifier.issn1875-6638
dc.identifier.issue5
dc.identifier.pmid36567289
dc.identifier.scopus2-s2.0-85153854470
dc.identifier.scopusqualityQ3
dc.identifier.startpage485
dc.identifier.urihttps://doi.org/10.2174/1573406419666221222143530
dc.identifier.urihttps://hdl.handle.net/20.500.12418/30492
dc.identifier.volume19
dc.identifier.wosWOS:001004020500008
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherBentham Science Publ Ltd
dc.relation.ispartofMedicinal Chemistry
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectHydrazone
dc.subjectbenzimidazole
dc.subjectcarbonic anhydrase I
dc.subjectcarbonic anhydrase II
dc.subjectMTT
dc.subjectmolecular docking
dc.titleSynthesis and Molecular Docking of New N-Acyl Hydrazones-Benzimidazole as hCA I and II Inhibitors
dc.typeArticle

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