The landscape of nature-derived antimalarials-potential of marine natural products in countering the evolving Plasmodium

Abstract

Malaria poses several challenges to the global research community on both diagnostic and therapeutic fronts. Most prominent of them are deletion of target genes (pfhrp2/3) used in rapid diagnostic tests (RDTs) and the emergence of resistance against frontline antimalarials by the evolving parasite. Exploration of novel therapeutics for malaria in view of limited vaccine options is a promising resort for malaria control and elimination. The scope of marine-derived chemotherapeutics is exciting, with a significant number of FDA-approved drugs or therapeutic leads under clinical trials for other diseases. This review article discusses the significant antimalarial potential of marine-derived natural products extracted from diverse biota including sponges, bacteria, sea hare and algae etc. Bioassay-guided fractionation of raw extracts from marine organisms for lead identification and further structural characterization of purified compounds compose a sustainable marine-derived drug discovery pipeline; which can be particularly diverted towards the exploration of antimalarials. It is to be noted that the Indian peninsula is largely unexplored, particularly for antimalarials screening; which has a huge marine biodiversity owing to the three distinct water bodies- Bay of Bengal, Indian Ocean and Arabian sea. This review also envisions a collaborative initiative to explore the potential of marine natural products in an economically feasible manner.

Marine organisms as potential sources of natural products for the prevention and treatment of malaria

“…97,98 Currently, plakortin is among pre-clinically investigated antiplasmodial candidates. 99 On the other side, plakortide L (99), was extracted from a Jamaican sponge Plakortis sp. 97,98 Plakortide O (100) and plakortide P (101), were isolated from plakortis halichondrioides, presented mild antimalarial activity in vitro (IC 50 > 0.023 mM).…”

“…109 Homogentisic acid is among pre-clinically investigated antiplasmodial candidates. 99 Furthermore, (S)-curcuphenol ( 120) is a sesquiterpene phenol isolated from the Jamaican sponge Didiscus oxeata, displayed in vitro activity against D6 and W2 strains of P. falciparum (MIC = 0.017 and 0.008 mM, respectively). 110 (2Z,6R,8R,9E)[3-ethyl-5-(2-ethyl-hex-3-enyl)-6-methyl-5H-furan-2-ylidene]-acetic acid methyl ester (121), a polyketide was isolated from Plakortis angulospiculatus sponge.…”

“…Table 6 A list of marine-derived macrolides antimalarial drugs showing their IC 50 against various strains of Plasmodium sp., chemical structure and biogenic source Bromophycolides have been mentioned among drugs that are investigated in pre-clinical trials. 99…”

Mixed Alkyl/Aryl Phosphonates Identify Metabolic Serine Hydrolases as Antimalarial Targets

“…Natural products have long served as valuable sources for the discovery of potential drugs in P. falciparum (Prashar et al, 2022). Salinipostin A (SalA) belongs to a group of bioactive natural compounds known as cyclophostins, characterized by the presence of a bicyclic enolphosphate structure (Spilling, 2019).…”