Design, synthesis, and antitumor evaluation of novel methylene moiety-tethered tetrahydroquinoline derivatives

Abstract

Novel methylene-tethered tetrahydroquinolines (THQs) and cyclopenta[ b]pyridines were synthesized by one-pot multicomponent reactions of Mannich bases, enolizable ketones, and NH 4 OAc in water by an environmentally friendly K-10 montmorillonite clay-catalyzed reaction. The cytotoxic activities of 1-(2-methyl-8-methylene-5,6,7,8-tetrahydroquinolin-3-yl)ethanone (9a), ethyl 2-methyl-8-methylene-5,6,7,8-tetrahydroquinoline-3 carboxylate (9b), and 1-(2-methyl-7-methylene-6,7-dihydro-5 H -cyclopenta[ b]pyridin-3-yl)ethanone (11a) were tested against rat glioblastoma (C6), human breast cancer (MCF-7), prostate cancer (PC3), neuroblastoma (SH-SY5Y), and mouse fibroblast (L929) cell lines in a concentration-dependent (50–300 µM) and time-dependent (24–72 h) manner and expressed as IC 50 values. The results showed that compound 9a induced the lowest IC 50 values in all cell lines ranging from 111 ±1.1 µM to 128 ±1.3 µM when compared to 9b and 11a after 72 h. As an evaluation of antibacterial properties, a swarming motility assay was performed with the Pseudomonas aeruginosa PA01 strain and compound 9a showed higher inhibition of swarming motility.