Synthesis, carbonic anhydrase inhibitory activity, anticancer activity and molecular docking studies of new imidazolyl hydrazone derivatives

Abstract

A new series of imidazolyl hydrazone derivatives IA ( 1-12 ) were prepared from a condensation reaction between indoline-2,3-dione (isatin) and 2-benzylidenehydrazinecarboximidamide derivatives. The struc-ture of compounds was elucidated using various spectral techniques including FTIR, 1 H NMR, 13 C NMR, and HRMS. The proposed structure of IA-2 was determined by single-crystal X-ray analysis. Synthesized compounds were evaluated for their inhibitory action against carbonic anhydrase I and II isoenzymes (hCA I and hCA II), as well as cytotoxicity activity in a cancer cell line (HT-29) and a healthy cell line (NIH 3T3). Among them, some compounds exhibited remarkable CA inhibitory activities compared to a standard inhibitor with Ki values in the range of 13.434 +/- 3.278-522.549 +/- 360.720 nM for hCA I (Ki value for standard inhibitor = 271.15 +/- 74.620 nM) and 41.108 +/- 10.180-271.171 +/- 65.293 nM for hCA II (Ki value for standard inhibitor = 113.07 +/- 20.980 nM) and significant antiproliferative activity with less toxicity to a health cell line. In addition, the theoretical parameters of the bioactive molecules were calculated to establish their drug-likeness qualities and ADME/T analysis was carried out to examine the drug properties of the synthesized compounds.(c) 2022 Elsevier B.V. All rights reserved.