Navarrete-Carriola Diana V, Rivera Gildardo, Ortiz-Pérez Eyra, Paz-González Alma D, Martínez-Vázquez Ana Verónica, Aquino-González Laura Victoria, Argueta-Figueroa Liliana, Doyle Michael P, Moreno-Rodríguez Adriana
Laboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genόmica, Instituto Politécnico Nacional, Reynosa 88710, Mexico.
Department of Chemistry, The University of Texas at San Antonio, San Antonio, TX 78249, USA.
Metabolites. 2025 Aug 21;15(8):560. doi: 10.3390/metabo15080560.
: Worldwide, the number of cases of parasitic diseases has been increasing; however, available treatments have variable adverse effects and low efficacy, mainly in Neglected Tropical Diseases such as Chagas disease and Leishmaniasis. Therefore, the development of new and more effective antiparasitic drugs is important. Natural products are the source of secondary metabolites with different biological activities, such as antibacterial, anticancer, anti-inflammatory, and antiparasitic. : In this work, secondary metabolites (phenols and terpenes) from natural products were selected to be evaluated against the epimastigotes of NINOA and A1 strains of and the promastigotes of M379 strain and FCQEPS native isolate of . Additionally, their cytotoxicity and selectivity index were determined. : Eighteen secondary metabolites were evaluated in vitro against epimastigotes and promastigotes; additionally, their cytotoxicity on the J774.2 macrophage cell line was determined. : The compounds l-(-)-menthol (14, IC = 24.52 µM) and β-citronellol (11, IC = 21.54 µM) had higher trypanocidal activity than the reference drug (benznidazole) against NINOA and A1 strains of , respectively. On the other hand, -anisyl alcohol (4, IC = 34.89 µM) had higher leishmanicidal activity than the reference drug (glucantime) against M379 and the FCQEPS native isolate of . Finally, in silico, the determination of their pharmacokinetic and toxicological properties showed that they are promising candidates for oral and topical uses. : This study opens the possibility of using secondary metabolites as scaffolds for access to the development of new molecules for the treatment of parasite diseases.
在全球范围内，寄生虫病病例数量一直在增加；然而，现有的治疗方法有不同的副作用且疗效较低，主要体现在如恰加斯病和利什曼病等被忽视的热带病方面。因此，开发新的、更有效的抗寄生虫药物很重要。天然产物是具有不同生物活性的次生代谢物的来源，如抗菌、抗癌、抗炎和抗寄生虫活性。在这项工作中，从天然产物中选择次生代谢物（酚类和萜类），对克氏锥虫NINOA和A1菌株的上鞭毛体以及硕大利什曼原虫M379菌株和FCQEPS本地分离株的前鞭毛体进行评估。此外，还测定了它们的细胞毒性和选择性指数。对18种次生代谢物进行了体外抗上鞭毛体和前鞭毛体的评估；此外，还测定了它们对J774.2巨噬细胞系的细胞毒性。化合物l-(-)-薄荷醇（14，IC = 24.52 μM）和β-香茅醇（11，IC = 21.54 μM）分别对克氏锥虫NINOA和A1菌株具有比参考药物（苯硝唑）更高的杀锥虫活性。另一方面，对甲氧基苄醇（4，IC = 34.89 μM）对硕大利什曼原虫M379和FCQEPS本地分离株具有比参考药物（葡糖胺锑钠）更高的杀利什曼活性。最后，通过计算机模拟，对它们的药代动力学和毒理学性质的测定表明，它们是口服和局部用药的有前景的候选药物。这项研究开启了将次生代谢物用作开发治疗寄生虫病新分子的支架的可能性。
