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.
[http://dx.doi.org/10.4155/fmc-2017-0149] [PMID: 29098865]
[http://dx.doi.org/10.1039/C6MD00479B] [PMID: 30108703]
[http://dx.doi.org/10.1016/j.ejmech.2017.02.031] [PMID: 28231521]
[http://dx.doi.org/10.1016/j.ejmech.2009.03.035] [PMID: 19395129]
[http://dx.doi.org/10.1016/j.bmcl.2012.01.052] [PMID: 22325950]
[http://dx.doi.org/10.1016/1056-8727(96)00113-4] [PMID: 8807467]
[http://dx.doi.org/10.1016/j.ejmech.2018.03.083] [PMID: 29626797]
[http://dx.doi.org/10.1016/j.bioorg.2012.08.002] [PMID: 23064124]
[http://dx.doi.org/10.3109/14756366.2014.940935] [PMID: 26095345]