Synthesis, anti-parasitic activity and QSAR study of a new library of polysubstituted tetrahydronaphtho[1,2- b ]azepines

AbstractA new series of twenty two 2-exo-aryl(heteroaryl)-1,4-epoxytetrahydronaphtho[1,2-b]azepines8–10 and eighteencis-2-aryl(heteroaryl)-4-hydroxytetrahydronaphtho[1,2-b]azepines11–13 were synthesized, and most of them were tested for their ability to inhibit the in vitro growth of the extracellular forms ofTrypanosoma cruzi andLeishmania infantum parasites. Cell toxicity was also determined on Vero and THP-1 mammalian cells. Seventeen compounds exhibited potent activity against the epimastigotes (IC50 lower than 20  µM), without cytotoxicity on Vero cells. Ten compounds also showed remarkable anti-leishmanial properties against the promastigote form of the parasite (IC50 lower than 20  µM), but most of them were found cytotoxic for HTP-1 cells. We have also performed a quantitative structure activity relationship analysis by means of the multivariate lineal regression (MLR) technique with a family of ninety-four tetrahydro-1-benzazepine and tetrahydronaphtho[1,2-b]azepine derivatives with anti-parasitic activity. The aim of this study is to develop a tool that permits us to elucidate the structural features, which influence in the bioactivity of these compounds. The QSAR prediction models forTrypanosoma cruzi andLeishmania infantum were acceptable with a correlation coefficient values (R) of 0.668 and 0.852, respectively, in the prediction of those activities.
Source: Medicinal Chemistry Research - Category: Chemistry Source Type: research