Winter Isabel, Lockhauserbäumer Julia, Lallinger-Kube Gertrud, Schobert Rainer, Ersfeld Klaus, Biersack Bernhard
Laboratory of Molecular Parasitology, Department of Genetics, University of Bayreuth, 95440 Bayreuth, Germany.
Organic Chemistry Laboratory, University of Bayreuth, 95440 Bayreuth, Germany.
Mol Biochem Parasitol. 2017 Jun;214:112-120. doi: 10.1016/j.molbiopara.2017.05.001. Epub 2017 May 15.
Two gold(I) N-heterocyclic carbene complexes 1a and 1b were tested for their anti-trypanosomal activity against Trypanosoma brucei parasites. Both gold compounds exhibited excellent anti-trypanosomal activity (IC=0.9-3.0nM). The effects of the gold complexes 1a and 1b on the T. b. brucei cytoskeleton were evaluated. Rapid detachment of the flagellum from the cell body occurred after treatment with the gold complexes. In addition, a quick and complete degeneration of the parasitic cytoskeleton was induced by the gold complexes, only the microtubules of the detached flagellum remained intact. Both gold compounds 1a and 1b feature selective anti-trypanosomal agents and were distinctly more active against T. b. brucei cells than against human HeLa cells. Thus, the gold complexes 1a and 1b feature promising drug candidates for the treatment of trypanosome infections such as sleeping sickness (human African Trypanosomiasis caused by Trypanosoma brucei parasites).
测试了两种金（I）氮杂环卡宾配合物1a和1b对布氏锥虫寄生虫的抗锥虫活性。两种金化合物均表现出优异的抗锥虫活性（IC = 0.9 - 3.0 nM）。评估了金配合物1a和1b对布氏锥虫细胞骨架的影响。用金配合物处理后，鞭毛迅速从细胞体脱离。此外，金配合物诱导了寄生虫细胞骨架的快速完全退化，只有脱离的鞭毛中的微管保持完整。金化合物1a和1b均为选择性抗锥虫剂，对布氏锥虫细胞的活性明显高于对人HeLa细胞的活性。因此，金配合物1a和1b是治疗锥虫感染如昏睡病（由布氏锥虫寄生虫引起的人类非洲锥虫病）的有前景的候选药物。
