Synthesis of Novel Alkyl Amide Functionalized Trifluoromethyl Substituted Furo/thieno Pyridine Derivatives: Their Anticancer Activity and CoMFA and CoMSIA Studies

A series of novel alkyl amide functionalized trifluoromethyl substituted furo/thieno pyridine derivatives 4a-h, 5a-d, and 6a-h were prepared starting from 2-oxo/thioxo-6-phenyl/thien-2-yl-4-(trifluoromethyl)-1,2-dihydropyridine-3-carbonitrile 1 on reaction with bromoethylacetate followed by reaction with different primary aliphatic amines, cyclic secondary amines, or l-amino acids under different set of conditions. All the synthesized compounds 4a-h, 5a-d, and 6a-h were screened for anticancer activity against four cancer cell lines such as HeLa-cervical cancer (CCL-2), COLO205-colon cancer (CCL-222), HepG2-liver cancer (HB-8065), and MCF7-breast cancer (HTB-22). Compounds 4g and 4h are found to have promising anticancer activity at micromolar concentration. CoMFA and CoMSIA methods were applied to derive 3D-QSAR models for alkyl amide tagged furo/thieno pyridine derivatives as potential anticancer inhibitors. 3D-QSAR models provided a strong basis for future rational design of more active and selective HeLa, COLO205, HepG2, and MCF-7 cell line inhibitors.