Abstract：
Neglected Tropical Diseases are a significant concern as they encompass various infections caused by pathogens prevalent in tropical regions. The limited and often highly toxic treatment options for these diseases necessitate the exploration of new therapeutic candidates. In the present study, the lignan methylpiperitol was isolated after several chromatographic steps from Persea fulva L. E. Koop (Lauraceae) and its leishmanicidal and trypanocidal activities were evaluated using in vitro and in silico approaches. The chemical structure of methylpiperitol was defined by NMR and MS spectral data analysis. The antiprotozoal activity of methylpiperitol was determined in vitro and indicated potency against trypomastigote forms of Trypanosoma cruzi (EC50 of 4.5±1.1 mM) and amastigote forms of Leishmania infantum (EC50 of 4.1±0.5 mM), with no mammalian cytotoxicity against NCTC cells (CC50>200 mM). Molecular docking studies were conducted using six T. cruzi and four Leishmania. The results indicate that for the molecular target hypoxanthine phosphoribosyl transferase in T. cruzi and piteridine reductase 1 of L. infatum, the methylpiperitol obtained better results than the crystallographic ligand. Therefore, the lignan methylpiperitol, isolated from P. fulva holds potential for the development of new prototypes for the treatment of Neglected Tropical Diseases, especially leishmaniasis.
摘要：
被忽视的热带病是一个重要的问题，因为它们包括由热带地区流行的病原体引起的各种感染。这些疾病的有限且通常是高毒性的治疗选择需要探索新的治疗候选物。在本研究中,经过几个色谱步骤从PerseafulvaL.E.Koop（Lauraceae）中分离出木酚素甲基胡椒糖醇，并使用体外和计算机方法评估了其杀利什曼和杀锥虫活性。甲基哌啶醇的化学结构由NMR和MS光谱数据分析确定。在体外确定了甲基哌啶醇的抗原生动物活性，并表明了对锥虫锥虫形式的效力（EC50为4.5±1.1mM）和婴儿利什曼原虫的阿马丝虫形式（EC50为4.1±0.5mM），没有哺乳动物对NCTC细胞的细胞毒性(CC50>200mM)。分子对接研究使用6个克氏虫和4个利什曼原虫进行。结果表明，对于Cruzi中的次黄嘌呤磷酸核糖转移酶和fatum的piteridine还原酶1的分子靶标，甲基哌啶醇获得了比晶体学配体更好的结果。因此,木脂素甲基哌啶醇，从P.fulva分离具有开发用于治疗被忽视的热带病的新原型的潜力，尤其是利什曼病.
