4-Arylthiosemicarbazide derivatives as a new class of tyrosinase inhibitors and anti- agents.

We report herein anti-proliferation effects of 4-arylthiosemicarbazides, with a cyclopentane substitution at 1 position, on highly virulent RH strain of . Among them, the highest anti- activity was found with the -iodo derivative. Further experiments demonstrated inhibitory effects of thiosemicarbazides on tyrosinase (Tyr) activity, and good correlation was found between percentage of Tyr inhibition and IC. To confirm the concept that thiosemicarbazides are able to disrupt tyrosine metabolism in tachyzoites, the most potent Tyr inhibitors were tested for their efficacy of growth inhibition. All of them significantly reduced the number of tachyzoites in the parasitophorous vacuoles (PVs) compared to untreated cells, as well as inhibited tachyzoites growth by impeding cell division. Collectively, these results indicate that compounds with the thiosemicarbazide scaffold are able to disrupt tyrosine metabolism in tachyzoites by deregulation of their crucial enzyme tyrosine hydroxylase (TyrH).