Molecular modelling design, synthesis and cytotoxic evaluation of certain substituted 2-(3,4,5-triacetoxybenzoylamino)benzo[d]thiazole and 2-(galloylamino)benzo[d]thiazole derivatives having potential topoisomerase-I inhibitory activity.

New 2-(3,4,5-triacetoxybenzoylamino)benzothiazoles (4a5f) and 2-(galloylamino)benzothiazoles (6a7f), were designed as topoisomerase-I inhibitors. Compare/fit studies between these molecules and the generated topoisomerase-I inhibitors hypothesis revealed that 4a5f have higher fitting values than (6a7f). Also, docking of 4a7f with the topoisomerase-I enzyme prioritized the higher activity of (4a5f) than (6a~7f). These molecules were synthesized and biologically evaluated for their in vitro cytotoxic activity against Hela and MCF7 human cancer cell lines in comparison to Camptothecin (topo-I inhibitor) and doxorubicin (topo-II inhibitors) as reference drugs. Such screening revealed that compounds 4d, 4e, 4h, 5b, 5c and 5e have comparable higher cytotoxic activity in both cultures than these reference drugs. The highest active molecule was 5f that gave 1.5 folds higher cytotoxic activity against Hela cell cultures and 1.9 folds higher activity against MCF7 cell lines than doxorubicin and 1.6 folds and 2.2 folds higher activity towards the two respective cultures than Camptothecin.