Laboratory of Medicinal Chemistry, Faculty of Medicine, University of Liege, Liege, Belgium.
Laboratory of Pharmacognosy, Faculty of Medicine, University of Liege, Liege, Belgium.
Curr Med Chem. 2021;28(30):6199-6233. doi: 10.2174/0929867328666210329112354.
Despite major advances in the fight against this parasitic disease, malaria remained a major cause of concern in 2021. This infection, mainly due to Plasmodium falciparum, causes more than 200 million cases every year and hundreds of thousands deaths in the developing regions, mostly in Africa. The last statistics show an increase in the cases for the third consecutive year; from 211 million in 2015, it has reached 229 million in 2019. This trend could be partially explained by the appearance of resistance to all the used antimalarials, including artemisinin. Thus, the design of new anti- Plasmodium compounds is an urgent need. For thousands of years, nature has offered humans medicines to cure their diseases or the inspiration for the development of new active principles. It then seems logical to explore the natural sources to find new molecules to treat this parasitosis.
Therefore, this review reports and analyzes the extracts (plants, bacteria, sponges, fungi) and the corresponding isolated compounds, showing antiplasmodial properties between 2013 and 2019.
Nature remains a major source of active compounds. Indeed, 648 molecules from various origins, mostly plants, have been reported for their inhibitory effect on Plasmodium falciparum. Among them, 188 scaffolds were defined as highly active with IC ≤ 5 μM, and have been reported here in detail. Moreover, the most active compounds showed a large variety of structures, such as flavonoids, triterpenes, and alkaloids. Therefore, these compounds could be an interesting source of inspiration for medicinal chemists; several of these molecules could become the next leads for malaria treatment.
尽管在抗击这种寄生虫病方面取得了重大进展，但疟疾仍是 2021 年的主要关注点。这种感染主要由恶性疟原虫引起，每年导致 2 亿多例病例，并在发展中地区造成数十万人死亡，主要在非洲。最新统计数据显示，病例数连续第三年上升；从 2015 年的 2.11 亿例增加到 2019 年的 2.29 亿例。这种趋势部分可以解释为所有已用抗疟药物（包括青蒿素）耐药性的出现。因此，设计新的抗疟化合物是当务之急。几千年来，大自然为人类提供了治疗疾病的药物，或者为开发新的有效成分提供了灵感。因此，探索自然来源以寻找治疗这种寄生虫病的新分子似乎是合乎逻辑的。
因此，本综述报告和分析了 2013 年至 2019 年具有抗疟活性的提取物（植物、细菌、海绵、真菌）和相应的分离化合物。
大自然仍然是活性化合物的主要来源。实际上，已经报道了 648 种来自不同来源的分子，主要是植物，它们对恶性疟原虫具有抑制作用。其中，188 种支架被定义为具有 IC≤5 μM 的高度活性，并在此详细报告。此外，最有效的化合物表现出各种结构，如黄酮类、三萜类和生物碱类。因此，这些化合物可能是药物化学家的一个有趣来源；其中一些分子可能成为疟疾治疗的下一个先导化合物。
