Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Farmacognosia, Buenos Aires, Argentina; CONICET - Universidad de Buenos Aires, Instituto de Química y Metabolismo del Fármaco (IQUIMEFA), Buenos Aires, Argentina.
Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Farmacognosia, Buenos Aires, Argentina.
Fitoterapia. 2023 Jun;167:105499. doi: 10.1016/j.fitote.2023.105499. Epub 2023 Apr 3.
Chagas disease, African trypanosomiasis and Leishmaniasis are neglected parasitic diseases which affect millions of people worldwide. In a previous work, we report the antiprotozoal activity of the dichloromethane extract of Mikania periplocifolia Hook. & Arn. (Asteraceae). The aim of this work was to isolate and identify the bioactive compounds present in the extract. The fractionation of the dichloromethane extract has led to the isolation of the sesquiterpene lactone miscandenin and the flavonoid onopordin, together with the sesquiterpene lactones mikanolide, dihydromikanolide and deoxymikanolide, which have previously shown antiprotozoal activity. Miscandenin and onopordin were assayed in vitro against Trypanosoma cruzi, T. brucei and Leishmania braziliensis. Miscandenin was active against T. cruzi trypomastigotes and amastigotes with IC values of 9.1 and 7.7 μg/ml, respectively. This sesquiterpene lactone and the flavonoid onopordin showed activity against T. brucei trypomastigotes (IC = 0.16 and 0.37 μg/ml) and L. braziliensis promastigotes (IC = 0.6 and 1.2 μg/ml), respectively. The CC values on mammalian cells were 37.9 and 53.4 μg/ml for miscandenin and onopordin, respectively. Besides, the pharmacokinetic and physicochemical properties of miscandenin were assessed in silico, showing a good drug-likeness profile. Our results highlight this compound as a promising candidate for further preclinical studies in the search of new drugs for the treatment of trypanosomiasis and leishmaniasis.
恰加斯病、非洲锥虫病和利什曼病是被忽视的寄生虫病，影响着全球数百万人。在之前的工作中，我们报告了 Mikania periplocifolia Hook. & Arn.（菊科）二氯甲烷提取物的抗原生动物活性。这项工作的目的是分离和鉴定提取物中存在的生物活性化合物。二氯甲烷提取物的分级分离导致分离出倍半萜内酯miscandenin 和黄酮类化合物 onopordin，以及以前显示出抗原生动物活性的倍半萜内酯 mikanolide、二氢 mikanolide 和去氧 mikanolide。miscandenin 和 onopordin 在体外针对 Trypanosoma cruzi、T. brucei 和 Leishmania braziliensis 进行了测试。Miscandenin 对 T. cruzi 锥虫和阿米巴的 IC 值分别为 9.1 和 7.7μg/ml。这种倍半萜内酯和黄酮类化合物 onopordin 对 T. brucei 锥虫（IC = 0.16 和 0.37μg/ml）和 L. braziliensis 前体（IC = 0.6 和 1.2μg/ml）均具有活性。对哺乳动物细胞的 CC 值分别为 37.9 和 53.4μg/ml。此外，还通过计算机评估了 miscandenin 的药代动力学和物理化学性质，显示出良好的药物样特征。我们的结果强调了该化合物作为进一步进行临床前研究的有前途的候选物，以寻找治疗锥虫病和利什曼病的新药物。
