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

Journal of Enzyme Inhibition and Medicinal Chemistry

Katarzyna Dzitko¹  Adrian Bekier¹  Lidia Węglińska²  Agata Paneth²  Piotr Paneth³ 

[1] Department of Molecular Microbiology, Faculty of Biology and Environmental Protection, University of Lodz;Department of Organic Chemistry, Faculty of Pharmacy, Medical University of Lublin;Institute of Applied Radiation Chemistry, Lodz University of Technology;

关键词: molecular docking;    sar analysis;    thiosemicarbazides;    toxoplasma gondii;    tyrosinase;   

DOI  :  10.1080/14756366.2021.1931164

来源: DOAJ

【 摘 要 】

We report herein anti-proliferation effects of 4-arylthiosemicarbazides, with a cyclopentane substitution at N1 position, on highly virulent RH strain of Toxoplasma gondii. Among them, the highest in vitro anti-Toxoplasma activity was found with the meta-iodo derivative. Further experiments demonstrated inhibitory effects of thiosemicarbazides on tyrosinase (Tyr) activity, and good correlation was found between percentage of Tyr inhibition and IC50Tg. To confirm the concept that thiosemicarbazides are able to disrupt tyrosine metabolism in Toxoplasma tachyzoites, the most potent Tyr inhibitors were tested for their efficacy of T. gondii 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 Toxoplasma tachyzoites by deregulation of their crucial enzyme tyrosine hydroxylase (TyrH).

【 授权许可】

Unknown