do Carmo Guilherme M, de Sá Mariângela F, Grando Thirssa H, Gressler Lucas T, Baldissera Matheus D, Monteiro Silvia G, Henker Luan C, Mendes Ricardo E, Stefani Lenita M, Da Silva Aleksandro S
Department of Biochemistry and Molecular Biology, Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, Brazil.
Department of Microbiology and Parasitology, Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, Brazil.
Exp Parasitol. 2019 Apr;199:47-51. doi: 10.1016/j.exppara.2019.02.016. Epub 2019 Feb 27.
The aim of this study was to evaluate in vitro the efficacy of cordycepin and pentostatin (alone or combined) against Trypanosoma cruzi, as well as the therapeutic efficiency of protocols of cordycepin and pentostatin combinations in mice experimentally infected with T. cruzi. In vitro, the cordycepin (3'-deoxyadenosine) and pentostatin (deoxycoformycin) exerted potent trypanocidal effect against T. cruzi (Colombian strain), similarly to benznidazole, which is the reference drug. For epimastigotes, the lethal dose of cordycepin capable of killing 50% (LD) and 20% (LD) of the parasites was 0.072 and 0.031 mg/mL, respectively and for trypomastigotes was 0.047 and 0.015 mg/mL, respectively. The combined use of cordycepin and pentostatin resulted in a LD and LD for epimastigotes of 0.068 and 0.027 mg/mL, respectively, as well as 0.056 and 0.018 mg/mL for trypomastigotes, respectively. In vivo, the combined use of cordycepin and pentostatin did not show the expected curative effect, however it was able to control the parasitema in the peak period. In summary, the combination of cordycepin and pentostatin showed no curative effect in mice infected by T. cruzi, despite the in vitro reduction of epimastigotes and trypomastigotes.
本研究的目的是在体外评估虫草素和喷司他丁(单独或联合使用)对克氏锥虫的疗效,以及虫草素和喷司他丁联合用药方案对实验感染克氏锥虫小鼠的治疗效果。在体外,虫草素(3'-脱氧腺苷)和喷司他丁(脱氧助间型霉素)对克氏锥虫(哥伦比亚株)具有强大的杀锥虫作用,与参考药物苯硝唑类似。对于前鞭毛体,能够杀死50%(LD)和20%(LD)寄生虫的虫草素致死剂量分别为0.072和0.031 mg/mL,对于锥鞭毛体分别为0.047和0.015 mg/mL。虫草素和喷司他丁联合使用时,前鞭毛体的LD和LD分别为0.068和0.027 mg/mL,锥鞭毛体分别为0.056和0.018 mg/mL。在体内,虫草素和喷司他丁联合使用未显示出预期的治愈效果,然而它能够在高峰期控制寄生虫血症。总之,尽管虫草素和喷司他丁在体外可减少前鞭毛体和锥鞭毛体,但它们联合使用对感染克氏锥虫的小鼠没有治愈效果。