Majumder Nilanjana, Banerjee Antara, Saha Samiran
Department of Biotechnology, Visva-Bharati, Santiniketan, 731235 West Bengal, India.
Department of Zoology, Bangabasi College, 19 Rajkumar Chakraborty Sarani, Kolkata, 700009 West Bengal, India.
Acta Trop. 2023 Apr;240:106846. doi: 10.1016/j.actatropica.2023.106846. Epub 2023 Jan 30.
Leishmaniases are considered among the most neglected yet dangerous parasitic diseases worldwide. According to the recent WHO report (Weekly Epidemiological Record, Sep, 2021), 200 countries and territories reported leishmanises cases in 2020; of which 89 (45%) for CL, and 79 (40%) for VL were endemic. Indian subcontinent (India, Bangladesh and Nepal), one of the three eco-epidemiological hotspots of VL, currently reported 18% of the total cases of VL worldwide. Eastern Mediterranean region and the Region of the Americas together reported >90% of the new CL cases, of which >80% were from Afghanistan, Algeria, Brazil, Colombia, Iraq, Pakistan and the Syrian Arab Republic. While considering the current therapeutic options, conventional anti-leishmanial drugs have long been proved to be toxic and/or expensive and have resulted in extensive drug resistance in India. Recent searches for novel anti-leishmanial drugs have led to find out the prime cellular targets and metabolic pathways to bridge the gap between the known facts and unexplored data. Cutting edge knowledge based drug designing has simplified the search for novel molecules with leishmanicidal efficacy by identifying ligand-receptor interactions and has accelerated the cost effective primary discovery of molecules through computational validation against Leishmaniases. This review focuses on the limitations of conventional drugs, and discusses the chemotherapeutic potential of many novel natural and synthetic anti-leishmanial agents reported since the last decade. It is also interpreted that some of the reported molecules might be tested singly or as a part of combinatorial therapy on pre-clinical and clinical level.
利什曼病被认为是全球最被忽视但却危险的寄生虫病之一。根据世界卫生组织最近的报告（《疫情周报》，2021年9月），2020年有200个国家和地区报告了利什曼病病例；其中89个（45%）为皮肤利什曼病，79个（40%）为内脏利什曼病流行地区。印度次大陆（印度、孟加拉国和尼泊尔）是内脏利什曼病三个生态流行病学热点地区之一，目前报告的内脏利什曼病病例占全球总数的18%。东地中海区域和美洲区域共报告了>90%的皮肤利什曼病新病例，其中>80%来自阿富汗、阿尔及利亚、巴西、哥伦比亚、伊拉克、巴基斯坦和阿拉伯叙利亚共和国。考虑到目前的治疗选择，传统的抗利什曼药物长期以来被证明有毒和/或昂贵，并在印度导致了广泛的耐药性。最近对新型抗利什曼药物的研究已找出主要细胞靶点和代谢途径，以弥合已知事实与未探索数据之间的差距。基于前沿知识的药物设计通过识别配体-受体相互作用简化了对具有杀利什曼原虫功效的新型分子的搜索，并通过针对利什曼病的计算验证加速了分子的经济高效初步发现。本综述重点关注传统药物的局限性，并讨论自过去十年以来报道的许多新型天然和合成抗利什曼药物的化疗潜力。还可以解读为，一些已报道的分子可能会在临床前和临床水平上单独进行测试或作为联合治疗的一部分进行测试。
