Herráez Rocío, Quesada Roberto, Dahdah Norma, Viñas Miguel, Vinuesa Teresa
Department of Pathology and Experimental Therapeutics, Medical School, University of Barcelona, 08021 Barcelona, Spain.
Departamento de Química, Universidad de Burgos, 09001 Burgos, Spain.
Pharmaceutics. 2021 May 12;13(5):705. doi: 10.3390/pharmaceutics13050705.
The aim of this work was to explore new therapeutic options against Chagas disease by the in vitro analysis of the biocidal activities of several tambjamine and prodiginine derivatives, against the CLB strain (DTU TcVI). The compounds were initially screened against epimastigotes. The five more active compounds were assayed in intracellular forms. The tambjamine MM3 and both synthetic and natural prodigiosins displayed the highest trypanocidal profiles, with IC values of 4.52, 0.46, and 0.54 µM for epimastigotes and 1.9, 0.57, and 0.1 µM for trypomastigotes/amastigotes, respectively. Moreover, the combination treatment of these molecules with benznidazole showed no synergism. Finally, oxygen consumption inhibition determinations performed using high-resolution respirometry, revealed a potent effect of prodigiosin on parasite respiration (73% of inhibition at ½ IC), suggesting that its mode of action involves the mitochondria. Moreover, its promising selectivity index (50) pointed out an interesting trypanocidal potential and highlighted the value of prodigiosin as a new candidate to fight Chagas disease.
本研究的目的是通过体外分析几种坦布胺和灵菌红素衍生物对CLB菌株（DTU TcVI）的杀生物活性，探索治疗恰加斯病的新方法。这些化合物最初针对无鞭毛体进行筛选。对五种活性最高的化合物进行了细胞内形式的检测。坦布胺MM3以及合成和天然灵菌红素表现出最高的杀锥虫活性，对无鞭毛体的IC值分别为4.52、0.46和0.54μM，对锥鞭毛体/无鞭毛体的IC值分别为1.9、0.57和0.1μM。此外，这些分子与苯硝唑联合治疗未显示协同作用。最后，使用高分辨率呼吸测定法进行的氧消耗抑制测定表明，灵菌红素对寄生虫呼吸有显著影响（在½IC时抑制率为73%），这表明其作用方式涉及线粒体。此外，其有前景的选择性指数（50）表明其具有有趣的杀锥虫潜力，并突出了灵菌红素作为对抗恰加斯病新候选药物的价值。
