Abstract
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.
Highlights
Protozoal parasite diseases Antiprotozoal marine alkaloids Synthetic approaches to antiprotozoal marine natural products Indole alkaloids Guanidine alkaloids Exocyclic guanidines Endocyclic guanidines Bromopyrrole alkaloids Thiazine alkaloids Miscellaneous alkaloids Opportunities for chemistry
Human African trypanosomiasis, Chagas disease and leishmaniasis are infectious diseases caused by protozoan parasites, which are transmitted to humans by insect vectors
Many of these compounds likely evolved as chemical defences for the producing organism, but whatever the basis of the antiprotozoal activities and selectivities of marine alkaloids, it is clear that many of these compounds could serve as an inspiration for the development of novel antiprotozoal chemical entities
Summary
Human African trypanosomiasis (sleeping sickness), Chagas disease and leishmaniasis are infectious diseases caused by protozoan parasites, which are transmitted to humans by insect vectors. Review treatments, which include adverse side effects (o en leading to patient compliance issues), limited efficacy or emerging resistance and, in certain cases, high cost and prolonged treatment regimens.. Review treatments, which include adverse side effects (o en leading to patient compliance issues), limited efficacy or emerging resistance and, in certain cases, high cost and prolonged treatment regimens.6–8 These challenges are compounded by socio-economic consequences for affected nations, which are o en among the least developed.. Following a discussion of the existing state of the art with respect to the diseases and their treatments, those marine alkaloids that have been evaluated for antiprotozoal bioactivity in the period 2000–2020 are described, with an emphasis on the most potent isolates. We discuss synthetic approaches to marine alkaloids, emphasising routes that offer the most efficient access to the important bioactive alkaloid scaffolds, and those that are well-suited to analogue design and synthesis
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