Metabolites from Marine Sponges and Their Potential to Treat Malarial Protozoan Parasites Infection: A Systematic Review

Abstract

Malaria is an infectious disease caused by protozoan parasites of the Plasmodium genus through the bite of female Anopheles mosquitoes, affecting 228 million people and causing 415 thousand deaths in 2018. Artemisinin-based combination therapies (ACTs) are the most recommended treatment for malaria; however, the emergence of multidrug resistance has unfortunately limited their effects and challenged the field. In this context, the ocean and its rich biodiversity have emerged as a very promising resource of bioactive compounds and secondary metabolites from different marine organisms. This systematic review of the literature focuses on the advances achieved in the search for new antimalarials from marine sponges, which are ancient organisms that developed defense mechanisms in a hostile environment. The principal inclusion criterion for analysis was articles with compounds with IC₅₀ below 10 µM or 10 µg/mL against P. falciparum culture. The secondary metabolites identified include alkaloids, terpenoids, polyketides endoperoxides and glycosphingolipids. The structural features of active compounds selected in this review may be an interesting scaffold to inspire synthetic development of new antimalarials for selectively targeting parasite cell metabolism.

Keywords: Plasmodium; antimalarial; malaria; resistance; sponge.

Figure 1

Flow diagram of literature search and selection criteria used in the present review adapted from PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis).

Figure 2

Number of published papers reporting the antimalarial activity of new compounds from marine sources or plants in the past 10 years.

Figure 3

Chemical class of compounds (259) identified in the reviewed articles (37).

Figure 4

Alkaloids from marine sponges with antimalarial effect revealed moderate inhibitory activity on P. falciparum protein kinases (PfPK5 and Pfnek-1) and P. falciparum enoyl-ACP reductase (PfFabI).

Figure 5

Meroterpenes from a marine sponge with antimalarial effect revealed inhibitory activity on P. falciparum protein kinase (Pfnek-1) and P. falciparum farnesyl transferase.

Figure 6

Histogram of related mechanisms of action for each chemical compound class in different cell models indicated by the literature.