15β-Senecioyl-oxy-ent-kaur-16-en-19-oic Acid, a Diterpene Isolated from Baccharis lateralis, as Promising Oral Compound for the Treatment of Schistosomiasis,Journal of Natural Products

当前位置： X-MOL 学术 › J. Nat. Prod. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

15β-Senecioyl-oxy-ent-kaur-16-en-19-oic Acid, a Diterpene Isolated from Baccharis lateralis, as Promising Oral Compound for the Treatment of Schistosomiasis
Journal of Natural Products ( IF 3.3 ) Pub Date : 2020-11-25 , DOI: 10.1021/acs.jnatprod.0c01050
Deborah P Sessa ₁ , Ana C Mengarda ₂ , Paula E Simplicio ₂ , Guilherme M Antar ₃ , João Henrique G Lago ₁ , Josué de Moraes ₂

Affiliation

Praziquantel is the only available drug to treat schistosomiasis, and therefore, urgent studies must be performed to identify new anthelmintic agents. This study reports the anthelmintic evaluation of two related ent-kaurane diterpenes isolated from aerial parts of Baccharis lateralis (Asteraceae), ent-kaur-16-en-19-oic acid (1) and 15β-senecioyl-oxy-ent-kaur-16-en-19-oic acid (2) against Schistosoma mansoni in vitro and in a murine model of schistosomiasis. Both compounds exhibited in vitro activity with lethal concentration 50% (LC₅₀) values of 26.1 μM (1) and 11.6 μM (2) as well as reduced toxicity against human cell lines, revealing a good selectivity profile, mainly with compound 2 (selectivity index > 10). Compound 2 also decreased egg production and caused morphological alterations in the parasite reproductive system. In mice infected with S. mansoni, oral treatment with compound 2 at 400 mg/kg, the standard dose used in this model of schistosomiasis, caused a significant reduction in a total worm burden of 61.9% (P < 0.01). S. mansoni egg production, a key mechanism for both transmission and pathogenesis, was also markedly reduced. In addition, compound 2 achieved a significant reduction in hepatosplenomegaly. Therefore, the diterpene 15β-senecioyl-oxy-ent-kaur-16-en-19-oic acid (2) has an acceptable cytotoxicity profile and is orally active in a murine schistosomiasis model.

中文翻译：

15β-Senecioyl-oxy-ent-kaur-16-en-19-oic Acid，一种从 Baccharislateralis 中分离的二萜，作为治疗血吸虫病的有前景的口服化合物

吡喹酮是唯一可用于治疗血吸虫病的药物，因此，必须进行紧急研究以确定新的驱虫剂。本研究报告了从Baccharislateralis (菊科)地上部分分离的两种相关ent -kaurane 二萜的驱虫评估，ent -kaur-16-en-19-oic acid ( 1 ) 和 15β-senecioyl-oxy- ent -kaur- 16-en-19-oic 酸 ( 2 )在体外和在血吸虫病鼠模型中对抗曼氏血吸虫。两种化合物均表现出体外活性，致死浓度 50% (LC ₅₀ ) 值为 26.1 μM ( 1 ) 和 11.6 μM (2 ) 以及对人类细胞系的毒性降低，显示出良好的选择性特征，主要是化合物2 (选择性指数 > 10)。化合物2还降低了产卵量并导致寄生虫生殖系统的形态学改变。在感染了曼氏血吸虫的小鼠中，用400 毫克/千克的化合物2口服治疗，这是血吸虫病模型中使用的标准剂量，导致总蠕虫负担显着减少 61.9% ( P < 0.01)。S. mansoni产蛋量是传播和发病的关键机制，也显着减少。此外，化合物2肝脾肿大明显减轻。因此，二萜 15β-senecioyl-oxy- ent -kaur-16-en-19-oic acid ( 2 ) 具有可接受的细胞毒性特征，并且在鼠血吸虫病模型中具有口服活性。

更新日期：2020-12-24

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南