Glycosidases play an important role in a wide range of physiological and pathological conditions, and have become potential targets for the discovery and development of agents useful for the treatment of diseases such as diabetes,
cancer,
influenza, and even
AIDS. In this study, several
benzimidazole derivatives were prepared from
o-phenylenediamine and aromatic and heteroaromatic carboxaldehydes in very good yields, using
PdCl2(CH3CN)2 as the most efficient catalyst. Synthesized compounds were assayed for their activity on yeast and rat intestinal
alpha-glucosidase inhibition and cytotoxic activity against colon
carcinoma cell line HT-29. Compound 3e exhibited 95.6% and 75.3% inhibition of yeast and rat intestinal
alpha-glucosidase enzyme, while showing 74.8% cytotoxic activity against the HT-29 cell line at primary screening concentrations of 2.1 mM for yeast and rat intestinal
alpha-glucosidase enzyme and 0.2 mM for cytotoxic activity against the HT-29 cell line, respectively. Compound 3c displayed 76% and 34.4% inhibition of yeast and rat intestinal
alpha-glucosidase enzyme, and 80.4% cytotoxic activity against the HT-29 cell line at similar primary screening concentrations. The IC50 value for the most potent intestinal
alpha-glucosidase inhibitor compound 3e was found to be 99.4 microM. The IC50 values for the most active cytotoxic compounds 3c and 3e were 82 microM and 98.8 microM, respectively. Both compounds displayed significant
antihyperglycemic activity in
starch-induced
postprandial hyperglycemia in rats. This is the first report assigning yeast and rat intestinal
alpha-glucosidase enzyme inhibition, cytotoxic activity against the HT-29 cell line, and
antihyperglycemic activity to
benzimidazole compounds 3c and 3e.