Sección de Estudios de Posgrado e Investigación, Escuela Nacional de Medicina y Homeopatía, Instituto Politécnico Nacional, Ciudad de México, Mexico.
Mini Rev Med Chem. 2022;22(20):2661-2677. doi: 10.2174/1389557522666220404090429.
Leishmaniasis and trypanosomiasis are diseases that affect public health worldwide due to their high incidence, morbidity, and mortality. Available treatments are costly, prolonged, and toxic, not to mention the problem of parasite resistance. The development of alternative treatments is justified and polyphenols show promising activity.
The main aim of this mini-review was to analyze the most promising phenolic compounds with reported antileishmanial and antitrypanosomal activity as well as their mechanisms of action.
We found that the mode of action of these natural compounds, mainly lignans, neolignans, and flavonoids depends on the organism they act on and includes macrophage activation, induction of morphological changes such as chromatin condensation, DNA fragmentation, accumulation of acidocalcisomes, and glycosomes, Golgi damage and mitochondrial dysfunction as well as negative regulation of mitochondrial enzymes and other essential enzymes for parasite survival such as arginase. This gives a wide scope for future research toward the rational development of anti-kinetoplastid drugs.
Although the specific molecular targets, bioavailability, route of administration, and dosages of some of these natural compounds need to be determined, polyphenols and their combinations represent a very promising and safe strategy to be considered for use against Leishmania spp and Trypanosoma spp. In addition, these compounds may provide a scaffold for developing new, more potent, and more selective antiprotozoal agents.
利什曼病和锥虫病是全球性的公共卫生疾病,因为它们的发病率、发病率和死亡率都很高。现有的治疗方法成本高、时间长且有毒,更不用说寄生虫耐药性的问题了。开发替代疗法是合理的,多酚显示出有希望的活性。
本小型综述的主要目的是分析具有报道的抗利什曼原虫和抗锥虫活性的最有前途的酚类化合物及其作用机制。
我们发现,这些天然化合物(主要是木脂素、新木脂素和类黄酮)的作用方式取决于其作用的生物体,包括巨噬细胞激活、诱导染色质浓缩、DNA 断裂、积累酸钙体和糖体、高尔基体损伤和线粒体功能障碍以及负调节线粒体酶和其他对寄生虫生存至关重要的酶,如精氨酸酶。这为未来针对合理开发抗原生动物药物的研究提供了广阔的前景。
尽管需要确定某些天然化合物的特定分子靶标、生物利用度、给药途径和剂量,但多酚及其组合代表了一种非常有前途和安全的策略,可以考虑用于治疗利什曼原虫和锥虫。此外,这些化合物可能为开发新型、更有效和更具选择性的抗原生动物药物提供一个支架。