Shaha Chandrima
Division of Infectious Diseases and Immunology, Indian Institute of Chemical Biology, Kolkata, India.
Expert Rev Mol Med. 2025 Mar 26;27:e15. doi: 10.1017/erm.2025.8.
The global incidences of leishmaniasis are increasing due to changing environmental conditions and growing poverty. Leishmaniasis, caused by the parasite, presents itself in six different clinical forms, the cutaneous and the visceral diseases being the most prevalent. While the cutaneous form causes disfigurement, the visceral form could be fatal if not treated. With no available vaccines combined with serious side effects of current medications and emerging drug resistance, it is crucial to discover new drugs whether as novel compounds or as repurposed existing pharmaceuticals. In the realm of drug development, mitochondria are recognized as important pharmacological targets due to their critical role in energy control, which, when disrupted, leads to irreversible cell damage. Certain plant-based compounds able to target the parasite mitochondrion, have been studied for their potential anti-leishmanial effects.
These compounds have shown promising effects in eliminating the parasite. Artemisinin and chloroquine, two anti-malarial drugs that target mitochondria, exert strong anti-leishmanial effectiveness in both cultures and animal models. Quinolones, coumarins and quercetin are other compounds with leishmanicidal properties, which disrupt mitochondrial activity to effectively eliminate parasites in animal models of the disease and could be considered as potential drugs.
Therefore, plant-based compounds hold promise as potential candidates for anti-leishmanial drug development.
由于环境条件变化和贫困加剧,全球利什曼病发病率正在上升。利什曼病由寄生虫引起,有六种不同的临床形式,其中皮肤型和内脏型最为常见。皮肤型会导致毁容,而内脏型若不治疗可能致命。由于没有可用疫苗,加上现有药物副作用严重且出现耐药性,发现新药(无论是新型化合物还是现有药物的重新利用)至关重要。在药物研发领域,线粒体因其在能量控制中的关键作用而被视为重要的药理学靶点,线粒体功能紊乱会导致不可逆的细胞损伤。某些能够靶向寄生虫线粒体的植物性化合物,已针对其潜在的抗利什曼原虫作用进行了研究。
这些化合物在消除寄生虫方面显示出有前景的效果。青蒿素和氯喹这两种靶向线粒体的抗疟药物,在体外培养和动物模型中均具有很强的抗利什曼原虫效力。喹诺酮类、香豆素类和槲皮素是其他具有杀利什曼原虫特性的化合物,它们会破坏线粒体活性,从而在该疾病的动物模型中有效消除寄生虫,可被视为潜在药物。
因此,植物性化合物有望成为抗利什曼原虫药物研发的潜在候选物。