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Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

Research Article

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

Author(s): Kaan Küçükoğlu, Ulviye Acar Çevik*, Hayrunnisa Nadaroglu, Ismail Celik, Ayşen Işık, Hayrani Eren Bostancı, Yusuf Özkay and Zafer Asım Kaplancıklı

Volume 19, Issue 5, 2023

Published on: 20 January, 2023

Page: [485 - 494] Pages: 10

DOI: 10.2174/1573406419666221222143530

open access plus

Abstract

Background: 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 1H NMR, 13C 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 μM (hCA I) and 4.334-2.188 μM (hCA II). Inhibition types and Ki values of the compounds were determined. The Ki values of the compounds were 5.44 ± 0.14 μM-0.299 ± 0.01 μM (hCA I) and 3.699 ± 0.041 μM-1.507 ± 0.01 μM (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 μM. Accordingly, the type of inhibition was noncompetitive and the Ki value was 0.299 ± 0.01 μM.

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.

Keywords: Hydrazone, benzimidazole, carbonic anhydrase I, carbonic anhydrase II, MTT, molecular docking.

Graphical Abstract
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