Evaluation of Some Antidepressants as Inhibitors of Thioredoxin Reductase Enzyme, which is an Anticancer Target

Thioredoxin reductase (TrxR) is an enzyme that is involved in many metabolic pathways from detoxification to reduction of radicals by catalyzing the reduction of thioredoxin, and is therefore associated with many physiological processes, including cancer. Inhibitors of this enzyme are considered anticancer targets. In past studies, some antidepressants have been found to have anticancer effects through various mechanisms, and therefore the reuse of antidepressants as anticancer drugs has attracted the attention of researchers. In this study, it was aimed to investigate the inhibition effect of some antidepressants (neferine (1), amoxapine (2), mirtazapine (3), agomelatine (4), trazodone hydrochloride (5), amitrptyline hydrochloride (6)) on cytosolic rat liver TrxR activity. The inhibition effects of these molecules were determined by IC50 and Ki values. 1 (IC50:220 µM, Ki: 1.3±0.79 µM), 2 (IC50:337 µM, Ki: 5.2±2.1 µM), 3 (IC50:487 µM, Ki: 5.6±1.99 µM) and 4 (IC50: 545 µM, Ki: 7.0±1.83 µM) exhibited potent inhibition effect on cytosolic rat liver TrxR. As a result, it was hoped that these results might contribute to both explaining the anticancer mechanism of these antidepressants and synthesizing new TrxR inhibitors with anticancer effects