In vitro Inhibition Profiles and Molecular Docking Analysis of Benzohydrazide Derivatives on Red Blood Cell Carbonic Anhydrases Isozymes

Abstract

Background: Carbonic anhydrases (CAs, EC 4.2.1.1) are metalloenzymes that contain zinc ions on the active side and convert carbon dioxide to bicarbonate in metabolism. Human CA-I and CA-II, which are the most abundant CA isozymes in erythrocytes, have been therapeutic targets in the treatment of glaucoma, hypertension, ulcer, osteoporosis, and, neurological disorders. Benzohydrazides are biologically active compounds, and their various pharmacological effects have been reported.

Aim: In light of this, the objective of this study was to investigate the in vitro effects of benzohydrazide derivatives on the activities of hCA-I and hCA-II, determine the compounds as selective inhibitors for these isoenzymes, and estimate the inhibition mechanism through molecular docking studies.

Methods: In this work, we synthesized the 10 different derivatives of benzohydrazide containing various functional group of different positions.

Results: As a result, all benzohydrazide derivatives inhibited both isozymes in vitro and 2-amino 3- nitro benzohydrazide (10) was found to be the most efficient inhibitor of both hCA isozymes with the IC₅₀ values of 0.030 and 0.047 μM, respectively. In the molecular docking studies, 3-amino 2- methyl benzohydrazide (3) had the lowest estimated free binding energies against hCA isozymes as -6.43 and -6.13 kcal/mol.

Conclusion: In this study, hCA-I & II isozymes were isolate from human erythrocytes. CA isozymes are one of these target enzymes. WBC hope that the benzohydrazide derivatives, can guide remedies targeting carbonic anhydrase.

Keywords: Carbonic anhydrase; drug-likeness; inhibition; isozymes; molecular docking; structure-activity relationship.