Laboratório de Fitoquímica, Departamento de Saúde, Universidade Estadual de Feira de Santana, 44036-900, Feira de Santana, BA, Brazil.
Laboratório de Bioprospecção Fitoquímica, Departamento de Química, Universidade Federal Rural de Pernambuco, 52171-900, Recife, PE, Brazil.
Chem Biodivers. 2024 Aug;21(8):e202400678. doi: 10.1002/cbdv.202400678. Epub 2024 Jul 31.
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 (EC of 4.5±1.1 mM) and amastigote forms of Leishmania infantum (EC of 4.1±0.5 mM), with no mammalian cytotoxicity against NCTC cells (CC>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.
被忽视的热带病是一个严重的问题，因为它们包括由热带地区流行的病原体引起的各种感染。这些疾病的治疗选择有限且往往毒性很高，因此需要探索新的治疗候选物。在本研究中，从番石榴（番石榴科）中经过多次色谱步骤分离出木质素甲基哌啶醇，并通过体外和计算方法评估其杀利什曼原虫和杀锥虫活性。通过 NMR 和 MS 光谱数据分析确定了甲基哌啶醇的化学结构。在体外测定了甲基哌啶醇的抗原生动物活性，表明对 Trypanosoma cruzi 的动基体形式（EC 为 4.5±1.1mM）和 Leishmania infantum 的无鞭毛体形式具有活性（EC 为 4.1±0.5mM），对 NCTC 细胞没有哺乳动物细胞毒性（CC>200mM）。使用六个 T. cruzi 和四个 Leishmania 进行了分子对接研究。结果表明，对于 T. cruzi 的次黄嘌呤磷酸核糖基转移酶和 L. infatum 的 piteridine 还原酶 1 的分子靶标，与结晶配体相比，甲基哌啶醇获得了更好的结果。因此，从番石榴中分离出的木质素甲基哌啶醇具有开发新的治疗被忽视热带病（特别是利什曼病）原型的潜力。
