New hydrazone derivatives: synthesis, characterization, carbonic anhydrase I-II enzyme inhibition, anticancer activity and <i>in silico</i> studies

A new series of hydrazone derivatives (<b>1a-1l</b>) 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 <b>1d</b> 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 <b>1d</b> was found to be the strongest inhibitor, with IC₅₀ values of 0.133 µM against hCA I. Also, compound <b>1l</b> 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 <b>1j</b> and <b>1l</b> exhibited the highest cytotoxicity on the HT29 cell, while compounds <b>1e</b>, <b>1g,</b> and <b>1l</b> showed the strongest cytotoxic effect on C6 cell line. Compound <b>1l</b>, which carries the methoxy substituent at the 3^rd 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.