Synthesis, cytotoxic evaluation, and in silico studies of substituted N-alkylbromo-benzothiazoles

In efforts to develop a new class of anticancer agents with improved efficacy and selective action, a series of N-alkylbromo-benzothiazoles were synthesized and evaluated for in vitro cytotoxic activity against various human cancer cell lines such as lung (A-549), prostate (PC-3), leukemia (THP-1), and colon (Caco-2). They were found to be highly active against prostate (PC-3) and leukemia (THP-1) cancer cells, moderately active against colon (Caco-2) cancer cells and less active against lung (A-549) cancer cells. Of the 12 compounds, two (11d, 11j) exhibit IC50 values of a parts per thousand currency sign 1 mu M against leukemia (THP-1) cancer cell lines. Compound 11l showed significant cytotoxic activity against the PC-3 (IC50 = 0.6 mu M), THP-1 (IC50 = 3 mu M) and Caco-2 cell lines (IC50 = 9.9 mu M), respectively. Docking study of the synthesized ligand was done on epidermal growth factor receptor using ArgusLab flexible docking, to determine their observed activity. Further QSAR investigations with stepwise multiple linear regression analysis were applied to find correlation between various physicochemical parameters and anticancer activity. The QSAR results showed that anticancer activity could be modeled with descriptors. The predictive ability of models was cross-validated by observation of the low residual activity values and adjusted coefficient of variation () obtained by leave-one-out technique.