New hydrazone derivatives: synthesis, characterization, carbonic anhydrase I-II enzyme inhibition, anticancer activity and in silico studies
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Ulviye Acar Cevik
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Hakan Ünver
Abstract
A new series of hydrazone derivatives (1a-1l) were prepared from a condensation reaction between different hydrazide derivatives and 3-formylbenzoic acid. Through the use of several spectral techniques, such as 1H-NMR, 13C-NMR, and elemental analysis, the structures of the compounds were clarified. The crystal structure of compound 1d was obtained by single-crystal X-ray crystallography. They were found to have inhibitory effects on the anticancer potentials and human carbonic anhydrase isoforms I and II. Compound 1d was found to be the strongest inhibitor, with IC50 values of 0.133 µM against hCA I. Also, compound 1l showed the highest inhibitory activity with IC50 values of 3.244 µM against hCA II. Moreover, their cytotoxic effects on rat glioma cell and colon adeno carcinoma cell lines were evaluated. According to the cytotoxicity results, compounds 1j and 1l exhibited the highest cytotoxicity on the HT29 cell, while compounds 1e, 1g, and 1l showed the strongest cytotoxic effect on C6 cell line. Compound 1l, which carries the methoxy substituent at the 3rd position on the phenyl ring, was effective against both cancer cells and showed the highest inhibitory effect on hCA II. The ADME/T properties and molecular docking of the molecules with the highest activity were examined.
Acknowledgments
“The authors acknowledge to Scientific and Technological Research Application and Research Center, Sinop University, Turkey, for the use of the Bruker D8 QUEST diffractometer.”
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Research ethics: Not applicable.
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Informed consent: Not applicable.
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Author contributions: All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by the authors. The synthesis and X-ray studies of the compounds were carried out by [Hakan Ünver[ and [Ulviye Acar Çevik]. Cytotoxicity test was performed by [Hayrani Eren Bostancı], carbonic anhydrase test was performed by [Nurten İrem Gedik], [Ümit M. Kocyigit]. Docking and ADME studies were also carried out by [Burak Tüzün]. All authors read and approved the final manuscript.
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Use of Large Language Models, AI and Machine Learning Tools: None declared.
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Conflict of interest: The author states no conflict of interest.
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Research funding: None declared.
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Data availability: Not applicable.
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