Abstract

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.

Methods: The designed rhodanines were synthesized via dithiocarbamate formation, cyclization and Knoevenagel condensation. The structures of the synthesized compounds were confirmed and analyzed by spectral studies.

Results: 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 structureactivity relationship (3D-QSAR) technique was accomplished to elucidate structure-activity relationships.

Conclusion: Based on the information derived from CoMSIA contour plots, some key features for increasing the activity of compounds have been identified and used to design new anti-cancer agents. The present developed CoMSIA model displayed good external predictability, r2pred of 0.841 and good statistical robustness.

Keywords: Rhodanine, Knoevenagel condensation, MCF-7 cells, anticancer activity, CoMSIA, 3D QSAR.