Synthesis and Characterization of New Hexahydroquinoline Derivatives, In Silico Determination of Their Inhibitory Effects on Transforming Growth Factor Beta (TGF-β) and Their Effects on Oxidative Stress In Vitro

Hypertension is the biggest risk factor for atherosclerosis, which is a chronic vascular inflammatory disease. Normal endothelial cellular functions are disturbed in atherosclerosis. 1,4-dihydropiridines (1,4-DHPs) are an important class of bioactive molecules. Studies on 1,4DHP ring system have come by a new dimension after nifedipine and later amlodipine were introduced. Since then, several modifications were experimented on 1,4-DHP ring and investigation of other pharmacological activities along with their cardiovascular effects has gained speed. Hexahydrokinolines, the analogues of 1,4-DHP, are now intensively investigated for their calcium channel blocking activities. In the recent years, their inhibitory effects on transforming growth factor beta (TGF-β), their anti-atherogenic and anti-inflammatory effects were also discovered. The aim of this study was to evaluate the effects of 1,4-DHP derivatives on TGF-β in silico. In addition, the cytotoxic and oxidative stress-producing effects of 1,4-DHP derivatives (with a general formula of alkyl 4-(2-fluoro-4-(trifluoromethyl) phenyl)-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate) were determined in mouse 3T3 fibroblast cells.