Özet:

Glutathione reductase enzyme (GR) is an important enzyme that catalyzes the formation of reduced glutathione (GSH) from oxidized glutathione (GSSG) and undertakes the task of maintaining the GSH/GSSG ratio in the body. This important task has made the inhibition of GR an important target in the treatment of many diseases. Therefore, it is very important to identify new GR inhibitors that can be used in drug design. In vitro anticancer studies of different 2-aminothiazole analogs have been shown to have potent inhibitory activities against a wide variety of human cancer cell lines, including lung, leukemia, breast, ovarian, kidney, melanoma, colon, CNS, and prostate. We investigated the inhibition effect of six thiazole derivatives, which contain an amino group at the C-2 position and used as a core structure in therapeutic applications, on GR isolated from fresh human erythrocytes. We determined the IC50 values of compounds 2-amino-4-(2,4-difluorophenyl) thiazole, 2-amino-4-(4-bromophenyl)thiazole, 2-amino-5-methyl-4-phenylthiazole, 2-amino-4-(5,6,7,8-tetrahydro-2-naphthyl)thiazole, 2-amino-4-(4-chlorophenyl)thiazole, 4-(3,4-difluorophenyl)-1,3-thiazole-2-amino 0,64 µM, 3,69 µM, 42,8 µM, 0,91 µM, 0,63 µM ve 21 µM respectively. Ki values were calculated as 0,006±0,00048 µM, 0,33±0,11 µM, 63,61±0,33 µM, 0,905±0,073 µM, 0,89±0,47 µM, 97,44 µM respectively. It was observed that 2-amino-4-(2,4-difluorophenyl) thiazole had the highest inhibition effect and 4-(3,4-difluorophenyl)-1,3-thiazol-2-amino had the lowest inhibition effect. It was observed that only 2-amino-4-(2,4-difluorophenyl)thiazole exhibited competitive inhibition, while other compounds exhibited non-competitive inhibition. Our study shows that these thiazole derivatives are potent GR inhibitors and can be used as a guide for the identification of new drug candidates.

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