Novel Hydrazide-Hydrazones Bearing a Benzimidazole Ring: Design, Synthesis, and Evaluation of Inhibitor Properties Against CA I and CA II Isozymes

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dc.authoridISIK, Aysen/0000-0002-1280-0019
dc.authoridcelik, ismail/0000-0002-8146-1663
dc.contributor.authorIsik, Aysen
dc.contributor.authorCevik, Ulviye Acar
dc.contributor.authorCelik, Ismail
dc.contributor.authorKucukoglu, Kaan
dc.contributor.authorNadaroglu, Hayrunnisa
dc.contributor.authorBostanci, Hayrani Eren
dc.contributor.authorOzkay, Yusuf
dc.date.accessioned2025-05-04T16:46:52Z
dc.date.available2025-05-04T16:46:52Z
dc.date.issued2024
dc.departmentSivas Cumhuriyet Üniversitesi
dc.description.abstractIn this study, we propose identifying potential novel compounds targeting carbonic anhydrase I and II. Herein, we have designed and synthesized new benzimidazole-hydrazide-hydrazones derivatives (4a-4r) to investigate the effects of these synthesized compounds on CA isoenzymes. The compounds' 1H NMR, 13C NMR, and HRMS spectra were used to confirm their chemical structures. The synthetic derivatives were screened for their inhibitory potential against carbonic anhydrase I and II by in vitro assay. These compounds have IC50 values of 3.727-1.493 mu M (hCA I) and 3.892-1.547 mu M (hCA II). Inhibition types and Ki values of the compounds were determined. The Ki values of the compounds were 3.006 +/- 0.17 mu M-0.356 +/- 0.0 mu M (hCA I) and 2.923 +/- 0.15 mu M-0.346 +/- 0.0 mu M (hCA II). Acetazolamide (AAZ) was used as the reference in the study. The most potent derivatives, a 4-methoxy derivative (compound 4k) and 4-(trifluoromethyl) derivative (compound 4g), than AAZ (IC50 = 2.26 mu M) and their IC50 values were found as 1.493 mu M and 1.675 mu M, respectively. Compared to AAZ, the other derivatives having more effect on hCA I were compounds 4b, 4e, 4l, 4m, 4n, and 4o. The compounds gave IC50 values of 1.743, 1.789, 1.933, 1.966, 1.983, and 1.986 mu M, respectively. Compounds 4a-4r found no more effective inhibitory activity against hCA II isozyme than AAZ (IC50 = 1.17 mu M). According to the in vitro test results, detailed protein-ligand interactions of the compounds 4b and 4k exhibited considerably low binding energies, suggesting strong interaction affinities against hCA I. In addition, the cytotoxic effects of the compounds on the L929 healthy cell line were evaluated.
dc.description.sponsorshipSelcuk University, Scientific Research Projects Commission [24401030]
dc.description.sponsorshipThis study was supported by Selcuk University, Scientific Research Projects Commission (Project Number: 24401030).
dc.identifier.doi10.1111/cbdd.70025
dc.identifier.issn1747-0277
dc.identifier.issn1747-0285
dc.identifier.issue6
dc.identifier.pmid39615042
dc.identifier.scopus2-s2.0-85210732891
dc.identifier.scopusqualityQ2
dc.identifier.urihttps://doi.org/10.1111/cbdd.70025
dc.identifier.urihttps://hdl.handle.net/20.500.12418/35375
dc.identifier.volume104
dc.identifier.wosWOS:001369924000001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherWiley
dc.relation.ispartofChemical Biology & Drug Design
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WOS_20250504
dc.subjectbenzimidazole
dc.subjectcarbonic anhydrase
dc.subjectdocking
dc.subjecthydrazide
dc.subjectHydrazone
dc.subjectsynthesis
dc.titleNovel Hydrazide-Hydrazones Bearing a Benzimidazole Ring: Design, Synthesis, and Evaluation of Inhibitor Properties Against CA I and CA II Isozymes
dc.typeArticle

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