Moreira Fernanda de Lima, Riul Thalita Bachelli, Moreira Marcela de Lima, Pilon Alan Cesar, Dias-Baruffi Marcelo, Araújo Márcio S S, Lopes Norberto Peporine, de Oliveira Anderson R M
Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto - SP, Brazil.
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto - SP, Brazil.
Planta Med. 2018 Oct;84(15):1141-1148. doi: 10.1055/a-0614-2680. Epub 2018 May 15.
Piperlongumine is an amide alkaloid found in Piperaceae species that shows a broad spectrum of biological properties, including antitumor and antiparasitic activities. Herein, the leishmanicidal effect of piperlongumine and its derivatives produced by a biomimetic model using metalloporphyrins was investigated. The results showed that IC values of piperlongumine in promastigote forms of and were 7.9 and 3.3 µM, respectively. The IC value of piperlongumine in the intracellular amastigote form of was 0.4 µM, with a selectivity index of 25. The piperlongumine biomimetic derivatives, Ma and Mb, also showed leishmanicidal effects. We also carried out an metabolic degradation study showing that Ma is the most stable piperlongumine derivative in rat liver microsome incubations. The results presented here indicate that piperlongumine is a potential leishmanicidal candidate and support the biomimetic approach for development of new antileishmanial derivatives.
荜茇宁是一种存在于胡椒科植物中的酰胺生物碱，具有广泛的生物学特性，包括抗肿瘤和抗寄生虫活性。在此，研究了荜茇宁及其通过使用金属卟啉的仿生模型产生的衍生物的杀利什曼原虫作用。结果表明，荜茇宁对前鞭毛体形式的杜氏利什曼原虫和热带利什曼原虫的IC值分别为7.9和3.3 μM。荜茇宁对杜氏利什曼原虫细胞内无鞭毛体形式的IC值为0.4 μM，选择性指数为25。荜茇宁的仿生衍生物Ma和Mb也表现出杀利什曼原虫作用。我们还进行了代谢降解研究，结果表明Ma是大鼠肝微粒体孵育中最稳定的荜茇宁衍生物。此处呈现的结果表明，荜茇宁是一种潜在的杀利什曼原虫候选物，并支持开发新型抗利什曼原虫衍生物的仿生方法。
