Yeni Hekzahidrokinolin Türevlerinin Sentezi, Karakterizasyonu, Sitotoksisite, İntrasellüler Ros Üretimi ve Enflamasyon Mediyatörlerine İnhibitör Etkilerinin Saptanması

Abstract

In this study, 15 compounds with the general structure of hexahydroquinoline-3-carboxylate, a condensed derivative of 1,4-DHP, which are expected to show inhibitory activity on inflammatory mediators, were synthesized. The compounds were obtained by reaction of 4-(difluoromethoxy)benzaldehyde, substituted/non-substituted 1,3-cyclohexadione derivatives and appropriate alkyl acetoacetate compounds in the presence of ammonium acetate as nitrogen source according to Hantszch synthesis method. The structures of the synthesized compounds were elucidated by IR, 1H-NMR, 13C-NMR and HRMS methods. X-ray diagrams of some compounds with suitable crystal forms were taken. The cytotoxic properties of the compounds were examined by MTT method in 3T3 cell line. Among the 15 compounds, the three compounds with the least decrease in cell viability were selected for further experiments. The effects of the selected compounds on the levels of reactive oxygen species (ROS), cytokines, complement pathway c3 and c9 regulatory proteins as a result of lipooxygenase (LPS)-induced inflammation in the 3T3 cell line were investigated. It was found that three selected compounds decreased the level of TGF- 1 and among these compounds, compound 3e was the most active compound on the related cytokine. Molecular modeling studies were performed to determine the interaction of compound 3e with molecular targets.