Synthesis, in vitro evaluation of cytotoxic properties, ros generation potentials and effects on inflammation mediators of hexahydroquinoline derivatives

In this study, novel 24 compounds with alkyl 2,6,6-trimethyl-4-(disubstituted phenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate (Compound 1a-1f, 2a-2f, 3a-3f and 4a-4f) structure which is expected to show anti-inflammatory activity on inflammatory mediators were synthesized. The compounds were obtained by the modified Hantzsch reaction of 4,4-dimethyl-1,3-cyclohexanedione and various alkyl acetoacetate and disubstituted benzaldehyde derivatives in the presence of ammonium acetate. The melting points of the synthesized compounds were determined and their structures were proved by IR, 1H-NMR, 13C-NMR and HRMS methods. The cytotoxic properties of the compounds at different concentrations were investigated by MTT method in 3T3 and HepG2 cell lines. Twelve compounds those exhibit minimum cytotoxic properties depending on cell viability values were selected for further biological activity assays. The effects of selected compounds on intracellular ROS levels and protein levels of inflammatory cytokines were measured in sandwich ELISA kits in HepG2 cell line. As a result of these experiments, it was found that compound 1b decreased intracellular ROS, IL-6 and IL-1β levels with a statistically significant difference.