Centre for Parasitology and Mycology, Instituto Adolfo Lutz, São Paulo, 01246-000, Brazil.
Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, UK.
Nat Prod Rep. 2021 Dec 15;38(12):2214-2235. doi: 10.1039/d0np00078g.
Covering: 2000 up to 2021Natural products are an important resource in drug discovery, directly or indirectly delivering numerous small molecules for potential development as human medicines. Among the many classes of natural products, alkaloids have a rich history of therapeutic applications. The extensive chemodiversity of alkaloids found in the marine environment has attracted considerable attention for such uses, while the scarcity of these natural materials has stimulated efforts towards their total synthesis. This review focuses on the biological activity of marine alkaloids (covering 2000 to up to 2021) towards Neglected Tropical Diseases (NTDs) caused by protozoan parasites, and malaria. Chemotherapy represents the only form of treatment for Chagas disease, human African trypanosomiasis, leishmaniasis and malaria, but there is currently a restricted arsenal of drugs, which often elicit severe adverse effects, show variable efficacy or resistance, or are costly. Natural product scaffolds have re-emerged as a focus of academic drug discovery programmes, offering a different resource to discover new chemical entities with new modes of action. In this review, the potential of a range of marine alkaloids is analyzed, accompanied by coverage of synthetic efforts that enable further studies of key antiprotozoal natural product scaffolds.
2000 年至 2021 年
天然产物是药物发现的重要资源,直接或间接地为人类药物的潜在开发提供了众多小分子。在众多天然产物类别中,生物碱具有丰富的治疗应用历史。海洋环境中生物碱的广泛化学多样性引起了人们对这些用途的极大关注,而这些天然材料的稀缺性刺激了对其全合成的努力。
本综述重点介绍了 2000 年至 2021 年间海洋生物碱针对原生动物寄生虫引起的被忽视热带病(NTDs)和疟疾的生物活性。化疗是恰加斯病、人类非洲锥虫病、利什曼病和疟疾的唯一治疗形式,但目前药物种类有限,往往会引起严重的不良反应、疗效或耐药性差异,或者成本高昂。天然产物支架已重新成为学术药物发现计划的重点,为发现具有新作用模式的新化学实体提供了不同的资源。在本综述中,分析了一系列海洋生物碱的潜力,并介绍了能够进一步研究关键抗原生动物天然产物支架的合成工作。