SAR Study, Molecular Property and In Silico study of Novel Tetrahydroquinolines bearing Trifluoromethyl Group for Anticancer, Antimalarial, Anti HIV Activities

PS Pradeep, NM Jagadeesh, HC Kiran Kumar, KM Mahadevan^*
Department of Post Graduate Studies and Research in Chemistry, School of Chemical Sciences, Kuvempu University, P. G. Centre, Kadur, Karnataka-577 548, India.

A B S T R A C T
A milder and efficient method was described for the synthesis of cis-1-(2-(4-(trifluoromethyl) phenyl)-1, 2, 3, 4-tetrahydroquinolin-4-yl) pyrrolidin-2-ones/azepan-2-ones (3a-d, 4a-d) via imino Diels-Alder reaction between N-(4-(trifluoromethyl) benzylidene) anilines and N-vinyl caprolactam/N-vinyl pyrrolidin-2-one. Structural activity prediction reveals that the compounds 3d and 4d exhibits high polarisazability and molar refractivity. The ADMET and molecular descriptors study shows good bio availability and drug score for compounds 3a-d and 4a-d. Further the, molecular docking studies against cancer, malaria and HIV proteins results shows that the compounds 3c and 3d exhibits strong interaction with active site amino acids Thr44, Asp196 and Lys198 with interaction energy of -13.6269 and -9.74528 kcal/mol against cancer protein, in comparison with interaction energy obtained for reference drug methotrexate which shows -14.0509 kcal/mol towards cancer protein. And compound 4c shows good interaction against HIV protein by forming three hydrogen bonds with energy -10.7222 kcal/mol. However, none of the synthesized compounds exhibits activity against malarial protein.
Keywords: Tetra hydroquinoline, SAR, Pharmacokinetic, Molecular docking, Anticancer, Antimalarial, Anti HIV.