Development of Novel Rhodanine Analogs as Anticancer Agents: Design, Synthesis, Evaluation and CoMSIA Study.
Background: A series of novel 5-substituted benzylidene rhodanine derivatives using four different amines were designed based on our previously developed CoMSIA (Comparative molecular similarity indices analysis) model for the anticancer activity. Method: The designed rhodanines were synthesised via dithiocarbamate formation, cyclization and Knoevenagel condensation. The synthesized compounds were analyzed by spectral studies to confirm their structures. Result: The synthesized rhodanines were investigated for in vitro anticancer activities and the analogs have displayed mild to significant cytotoxicity against MCF-7 breast cancer cells. The compounds with benzyloxy substitution at the fifth position of rhodanine ring (Compounds 20, 33 and 38) system showed significant cytotoxic activity against MCF-7 cells. CoMSIA, a three-dimensional quantitative structure-activity relationship (3D-QSAR) technique was accomplished to elucidate structure-activity relationships. Conclusions: Based on the information derived from CoMSIA contour plots, some key features for increasing the activity of compounds have been identified and have been used to design new anti-cancer agents. The present developed CoMSIA model displayed good external predictability r2pred of 0.841 and good statistical robustness.