利什曼病是一种寄生虫病,被归类为被忽视的热带病(NTD)。每一年,据信发生了70,000至100万例新病例。大约有90种沙蝇可以传播利什曼原虫寄生虫(超过20种),每年导致20,000至30,000人死亡。目前,利什曼病没有特定的治疗方法。处方药有几个缺点,包括高成本,具有挑战性的管理,毒性,和耐药性导致寻找毒性和选择性更低的替代治疗方法。引入植物成分等分子特征以寻找毒性较小的化合物是另一种有前途的方法。当前的综述根据天然植物化学物质中存在的核心环对合成化合物进行了分类,用于开发抗利什曼原剂(2020-2022)。考虑到合成类似物的毒性和局限性,天然化合物在有效性和安全性方面处于较高水平。合成的查耳酮化合物(化合物8;IC50:0.03μM,效力比两性霉素B高4.7倍;IC50:0.14μM),嘧啶(化合物56;针对热带乳杆菌;0.04μM和婴儿乳杆菌;0.042μM,与葡聚糖时间相比:热带乳杆菌;8.17μM和婴儿乳杆菌;8.42μM),喹唑啉和(化合物72;0.021μM,比米替福辛有效150倍)。与标准甲氧苄啶(IC50:20μM)相比,针对DHFR的靶向递送已由一种嘧啶化合物62证明,其针对大乳杆菌的IC50值为0.10μM(IC50:20μM)。该综述涵盖了来自合成和天然来源如查尔酮的抗利什曼原药的药用重要性,吡唑,香豆素,类固醇,和含生物碱的药物(吲哚,喹啉,吡啶,嘧啶,卡波林,吡咯,极光,和喹唑啉)。讨论了在合成化合物中引入天然植物成分中存在的核心环作为抗利什曼虫的努力,并讨论了它们的结构活性关系。该观点将支持药物化学家完善和指导新型分子的基于植物化学物质的抗利什曼原药的开发。
Leishmaniasis is a parasitic disease and categorised as a neglected tropical disease (NTD). Each year, between 70,0000 and 1 million new cases are believed to occur. There are approximately 90 sandfly species which can spread the Leishmania parasites (over 20 species) causing 20,000 to 30,000 death per year. Currently, leishmaniasis has no specific therapeutic treatment available. The prescribed drugs with several drawbacks including high cost, challenging administration, toxicity, and drug resistance led to search for the alternative treatment with less toxicity and selectivity. Introducing the molecular features like that of phytoconstituents for the search of compounds with less toxicity is another promising approach. The current review classifies the synthetic compounds according to the core rings present in the natural phytochemicals for the development of antileishmanial agents (2020-2022). Considering the toxicity and limitations of synthetic analogues, natural compounds are at the higher notch in terms of effectiveness and safety. Synthesized compounds of chalcones (Compound 8; IC50: 0.03 μM, 4.7 folds more potent than Amphotericin B; IC50: 0.14 μM), pyrimidine (compound 56; against L. tropica; 0.04 μM and L. infantum; 0.042 μM as compared to glucantime: L. tropica; 8.17 μM and L. infantum; 8.42 μM), quinazoline and (compound 72; 0.021 μM, 150 times more potent than miltefosine). The targeted delivery against DHFR have been demonstrated by one of the pyrimidine compounds 62 with an IC50 value of 0.10 μM against L. major as compared to the standard trimethoprim (IC50: 20 μM). The review covers the medicinal importance of antileishmanial agents from synthetic and natural sources such as chalcone, pyrazole, coumarins, steroids, and alkaloidal-containing drugs (indole, quinolines, pyridine, pyrimidine, carbolines, pyrrole, aurones, and quinazolines). The efforts of introducing the core rings present in the natural phytoconstituents as antileishmanial in the synthetic compounds are discussed with their structural activity relationship. The perspective will support the medicinal chemists in refining and directing the development of novel molecules phytochemicals-based antileishmanial agents.