Synthesis and in vitro study of redox properties of pyrrole and halogenated pyrrole derivatives

Abstract

The redox balance plays a crucial role in maintaining biological processes under normal conditions. Antioxidants inhibit and reduce harmful oxidation processes, while pro-oxidants can act as anti-cancer agents by promoting ROS-mediated cell death. The aim of this study is to compare the redox properties of seven newly synthesised tribromopyrrole derivatives with three novel and four previously synthesized non-halogenated analogues in an in vitro model (in human serum) and with exogenously induced oxidative stress. The obtained values of their oxy scores (OS) were compared and the result showed that four non-halogenated pyrrole derivatives with secondary amide group M2, M10, M11 and M12 have lower OS values than Trolox, a water-soluble analogue of vitamin E with proven antioxidant properties. All four compounds show strong resistance to oxidative stress, which is reflected in the maintenance of negative OS values when exposed to exogenous oxidative stress using TBH in the reaction mixture. This capability to resist invading ROS should be expected also in an endogenous environment, where constant prooxidant production takes place at a low, homeostatic level, but even more so in pathological conditions. The tribrominated derivative M15 showed prooxidant activity with a significantly higher OS value than all other compounds tested. The comparison of the dose-response of Trolox and the five compounds with the lowest OS also shows that compounds M2, M7 and M10 have better antioxidant activity than Trolox.