对 和 的抑菌活性研究。
Activity of the sesquiterpene lactone goyazensolide against and .
机构信息
Programa de Pós-Graduação em Ciências Farmacêuticas (CIPHARMA), Escola de Farmácia, Universidade Federal de Ouro Preto (UFOP), Campus Universitário Morro do Cruzeiro, Ouro Preto, CEP: 35400-000, MG, Brazil.
Programa de Pós-Graduação em Ciências Biológicas (CBIOL), Núcleo de Pesquisa em Ciências Biológicas (NUPEB), Universidade Federal de Ouro Preto (UFOP), Campus Universitário Morro do Cruzeiro, Ouro Preto, CEP: 35400-000, MG, Brazil.
出版信息
Parasitology. 2020 Jan;147(1):108-119. doi: 10.1017/S0031182019001276. Epub 2019 Sep 23.
BACKGROUND
The current drugs for Chagas disease treatment present several limitations.
METHODS
The sesquiterpene lactone goyazensolide (GZL) was evaluated regarding to cytotoxicity and trypanocidal activity against amastigotes, selectivity index (SI) in vitro, acute toxicity and anti-Trypanosoma cruzi activity in vivo.
RESULTS
The in vitro cytotoxicity in H9c2 cells was observed at doses >250 ng mL-1 of GZL and the SI were of 52.82 and 4.85 (24 h) and of 915.00 and 41.00 (48 h) for GZL and BZ, respectively. Nephrotoxicity and hepatotoxicity were not verified. Treatment with GZL of mice infected with CL strain led to a significant decrease of parasitaemia and total survival at doses of 1 and 3 mg kg-1 day-1 by oral and IV, respectively. This last group cured 12.5% of the animals (negativation of HC, PCR, qPCR and ELISA). Animals infected with Y strain showed significant decrease of parasitaemia and higher negativation in all parasitological tests in comparison to BZ and control groups, but were ELISA reactive, as well as the BZ group, but mice treated with 5.0 mg kg-1 day-1 by oral were negative in parasitological tests and survived.
CONCLUSION
GZL was more active against T. cruzi than benznidazole in vitro and presented important therapeutic activity in vivo in both T. cruzi strains.
背景
目前用于恰加斯病治疗的药物存在多种局限性。
方法
评估倍半萜内酯 goyazensolide（GZL）的细胞毒性和对阿米巴滋养体的杀锥虫活性、体外选择性指数（SI）、急性毒性和体内抗 Trypanosoma cruzi 活性。
结果
在 H9c2 细胞中观察到的体外细胞毒性在 GZL 剂量>250ngmL-1时出现，SI 分别为 52.82 和 4.85（24 小时）以及 915.00 和 41.00（48 小时）GZL 和 BZ。未发现肾毒性和肝毒性。用 GZL 治疗感染 CL 株的小鼠，通过口服和 IV 分别以 1 和 3mgkg-1day-1 的剂量给药，可显著降低寄生虫血症和总存活率。最后一组治愈了 12.5%的动物（HC、PCR、qPCR 和 ELISA 阴性）。与 BZ 和对照组相比，感染 Y 株的动物寄生虫血症显著降低，所有寄生虫学检测的阴性率更高，但与 BZ 组一样，ELISA 呈阳性，但经口给予 5.0mgkg-1day-1 的动物在寄生虫学检测中呈阴性并存活。
结论
GZL 在体外对 T. cruzi 的活性比苯并咪唑更强，并且在两种 T. cruzi 株的体内均具有重要的治疗活性。
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