Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (FCEyN-UBA) E Instituto de Química Biológica de La Facultad de Ciencias Exactas y Naturales (IQUIBICEN) CONICET, Ciudad de Buenos Aires, C1428EHA, Argentina.
Grupo Estudios Preclínicos Para El Desarrollo de Productos, Corporación de Innovación CIDEPRO, Medellín, Colombia.
Parasitol Res. 2024 Apr 18;123(4):185. doi: 10.1007/s00436-024-08199-w.
Leishmania braziliensis (L. braziliensis) causes cutaneous leishmaniasis (CL) in the New World. The costs and the side effects of current treatments render imperative the development of new therapies that are affordable and easy to administer. Topical treatment would be the ideal option for the treatment of CL. This underscores the urgent need for affordable and effective treatments, with natural compounds being explored as potential solutions. The alkaloid piperine (PIP), the polyphenol curcumin (CUR), and the flavonoid quercetin (QUE), known for their diverse biological properties, are promising candidates to address these parasitic diseases. Initially, the in vitro cytotoxicity activity of the compounds was evaluated using U-937 cells, followed by the assessment of the leishmanicidal activity of these compounds against amastigotes of L. braziliensis. Subsequently, a golden hamster model with stationary-phase L. braziliensis promastigote infections was employed. Once the ulcer appeared, hamsters were treated with QUE, PIP, or CUR formulations and compared to the control group treated with meglumine antimoniate administered intralesionally. We observed that the three organic compounds showed high in vitro leishmanicidal activity with effective concentrations of less than 50 mM, with PIP having the highest activity at a concentration of 8 mM. None of the compounds showed cytotoxic activity for U937 macrophages with values between 500 and 700 mM. In vivo, topical treatment with QUE daily for 15 days produced cured in 100% of hamsters while the effectiveness of CUR and PIP was 83% and 67%, respectively. No failures were observed with QUE. Collectively, our data suggest that topical formulations mainly for QUE but also for CUR and PIP could be a promising topical treatment for CL. Not only the ease of obtaining or synthesizing the organic compounds evaluated in this work but also their commercial availability eliminates one of the most important barriers or bottlenecks in drug development, thus facilitating the roadmap for the development of a topical drug for the management of CL caused by L. braziliensis.
巴西利什曼原虫（L. braziliensis）在新世界引起皮肤利什曼病（CL）。当前治疗方法的成本和副作用使得开发负担得起且易于管理的新疗法变得至关重要。局部治疗将是治疗 CL 的理想选择。这凸显了对负担得起且有效的治疗方法的迫切需求，天然化合物正被探索作为潜在的解决方案。生物碱胡椒碱（PIP）、多酚姜黄素（CUR）和类黄酮槲皮素（QUE）以其多样的生物特性而闻名，是解决这些寄生虫病的有前途的候选药物。最初，使用 U-937 细胞评估了化合物的体外细胞毒性活性，然后评估了这些化合物对巴西利什曼原虫的无鞭毛体的杀利什曼原虫活性。随后，使用处于静止期 L. braziliensis 前鞭毛体感染的金黄地鼠模型。一旦出现溃疡，用 QUE、PIP 或 CUR 制剂治疗金黄地鼠，并与用肌氨肽苷局部注射治疗的对照组进行比较。我们观察到，三种有机化合物在体外均表现出高杀利什曼原虫活性，有效浓度低于 50mM，其中 PIP 在 8mM 浓度下活性最高。在体内，用 QUE 进行为期 15 天的每日局部治疗，100%的金黄地鼠治愈，而 CUR 和 PIP 的有效性分别为 83%和 67%。QUE 没有失败的情况。总的来说，我们的数据表明，主要针对 QUE 的局部制剂，也包括 CUR 和 PIP 的局部制剂，可能是 CL 的一种有前途的局部治疗方法。不仅评估的有机化合物易于获得或合成，而且它们的商业可用性消除了药物开发中最重要的障碍或瓶颈之一，从而为开发用于管理由 L. braziliensis 引起的 CL 的局部药物铺平了道路。
