Determination of antioxidant capacities of some benzothiophene derivatives and their inhibition models on GSTP1-1 isozyme

With the formula C4H4S thiophene is located in the class which belongs to heterocyclic compounds that are composed of five member rings, with sulphur as heteroatom. This group of organic compounds has many pharmacologically active molecules. Benzothiophenes, as sulfur containing heterocyclic family, contains highly stable aromatic compounds that exhibit important physicochemical characteristics. They show broad range of biological/pharmacological activities such as anti-inflammatory, analgesic, anti-fungal, antidepressant etc. In this thesis project, two novel benzothiophene derivatives were investigated for their antioxidant capacities by the applications of four assays (DPPH, ABTS, galvenoxyl, and phosphomolybdenum) which were all based on different operating mechanisms. Derivative-1 and Derivative-2 demonstrated different levels of antioxidant capacities with respect to universal standards of trolox, ascorbic acid, and quercetin. Derivative-2 showed 2 times more antioxidant capacity than trolox in galvinoxyl assay. Derivative-1 was comparable with, especially quercetin, in phosphomolybdenum assay. Those two derivatives were subjected for their possible inhibitory effect on human GSTP1-1, which is one of the phase II drug metabolising enzymes performing the conjugation between glutathione and a various of substrates. According to kinetic calculations, Derivative-1 applied (full) uncompetitive inhibition, and Derivative-2 generated (partial) mix inhibition on this pure enzyme. As a conclusion, those novel benzothiophene derivatives have potential to be used as antioxidant agents, after detailed medical tests. On the other hand, some more derivatization is required for them to be better inhibitors of GSTP1-1. Keywords: Antioxidant capacity, Benzothiophene, Glutathione S-transferase P1-1, Inhibition.