Immunomodulatory and Antileishmanial Activity of Phenylpropanoid Dimers Isolated from Nectandra leucantha.
Immunomodulatory and Antileishmanial Activity of Phenylpropanoid Dimers Isolated from Nectandra leucantha.
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DOI：
10.1021/np500809a
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发表时间：
2015-04-24
影响因子：
5.1
通讯作者：
Tempone AG
中科院分区：
文献类型：
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作者：
da Costa-Silva TA;Grecco SS;de Sousa FS;Lago JH;Martins EG;Terrazas CA;Varikuti S;Owens KL;Beverley SM;Satoskar AR;Tempone AG
采用抗利什曼原虫生物测定指导的分馏法，从白花蜜桔嫩枝提取物中分离出三种苯丙素二聚体（1−3），其中包括两种新的代谢产物。体外抗寄生虫活性的分离的化合物对杜氏利什曼原虫寄生虫和哺乳动物的细胞毒性和免疫调节作用进行了评价。化合物1 - 3对巨噬细胞内的细胞内无鞭毛体有效，IC 50值分别为26.7、17.8和101.9 μM。针对腹腔巨噬细胞，评价了哺乳动物细胞毒性（以50%细胞毒性浓度（CC 50）表示）。化合物1和3在高达290 μM时没有毒性，而化合物2的CC 50值为111.2 μM。化合物1 - 3还抑制了疾病恶化细胞因子IL-6和IL-10的产生，但对L. donovani感染的巨噬细胞，表明这些化合物的抗利什曼原虫活性是通过NO非依赖性机制介导的。因此，这些新的天然产物可能代表有前途的支架药物设计研究的利什曼病。
Three phenylpropanoid dimers (1−3) including two new metabolites were isolated from the extract of the twigs of Nectandra leucantha using antileishmanial bioassay-guided fractionation. The in vitro antiparasitic activity of the isolated compounds against Leishmania donovani parasites and mammalian cytotoxicity and immunomodulatory effects were evaluated. Compounds 1−3 were effective against the intracellular amastigotes within macrophages, with IC50 values of 26.7, 17.8, and 101.9 μM, respectively. The mammalian cytotoxicity, given by the 50% cytotoxic concentration (CC50), was evaluated against peritoneal macrophages. Compounds 1 and 3 were not toxic up to 290 μM, whereas compound 2 demonstrated a CC50 value of 111.2 μM. Compounds 1−3 also suppressed production of disease exacerbatory cytokines IL-6 and IL-10 but had minimal effect on nitric oxide production in L. donovani-infected macrophages, indicating that antileishmanial activity of these compounds is mediated via an NO-independent mechanism. Therefore, these new natural products could represent promising scaffolds for drug design studies for leishmaniasis.