Imidazole-hydrazone derivatives: Synthesis, characterization, X-ray structures and evaluation of anticancer and carbonic anhydrase I-II inhibition properties

The nine new imidazole-hydrazone derivatives of Schiff base were synthesized from the condensation reactions of 1-methyl-1H-imidazole-2-carbaldehyde with various substituted-hydrazide derivatives. Structures of the final compounds (1 a-1 i) were characterized by using H-1 NMR, C-13 NMR spectroscopic techniques, elemental analysis, and crystal X-ray diffraction. The in vitro carbonic anhydrase I and II potentials of these synthesized were evaluated. The result suggests that compound 1 a, a 4-methoxy substituted analog with an IC50 of 0.949 & mu;M, was found to have the most potent hCA I inhibitory activity. Compounds 1 c, 1 d, and 1 h were the most potent compounds on hCA II with IC50 values of 3.330, 4.454, and 5.66 & mu;M, respectively. All compounds were examined for their cytotoxicity towards human colorectal adenocarcinoma cell (HT29) and rat glioma cell line (C6) compared to mouse fibroblast normal cell line (L929) using the MTT assay method. The compounds 1 a, 1 d, and 1 i exhibited significant antiproliferative activity with less toxicity to a health cell line. Consequently, compound 1 a could be the potential lead for emerging selective cytotoxic compounds directing hCA I. Compound 1 d could be the potential lead for emerging selective cytotoxic compounds directing hCA II.