Abstract
It is important to discover novel antimalarial pharmacophores because of the widespread emergence of Plasmodium falciparum isolates resistant to the available drugs. Secondary metabolites derived from microbes associated with marine invertebrates are a valuable resource for the discovery of novel drug leads. However, the potential of marine microbes as a source of antimalarials has not been explored. We investigated the promise of marine microorganisms for the production of antimalarial activities by testing 2365 diverse microbial extracts using phenotypic screening of a multidrug resistant chloroquine resistant P. falciparum strain. We conducted counter screening against mammalian cells for the 317 active extracts that exhibited more than 70% inhibition at 1 µg/mL. The screen identified 17 potent bioactive leads from a broad range of taxa. Our results establish that the marine microbiome is a rich source of antiplasmodial compounds that warrants in depth exploration.
Highlights
Over 40% of the global population currently resides in regions with malaria transmission
Extracts of Marine Microbes Used in Screening
Further work including large scale up of the culture is required to fully identify the structure of the compound. This project screened a subset of the Harbor Branch Marine Microbial Culture Collection for antiplasmodial activity
Summary
Over 40% of the global population currently resides in regions with malaria transmission. Even artemisinin combination therapy, which is the recommended treatment for malaria in the disease endemic countries, is showing an alarming spread of resistance in wide areas of Southeast Asia [2,3]. Given this alarming situation for malaria treatment options, it is important to discover new chemical leads for the generation of malaria therapeutics. Natural products have been an important source for the discovery of new drug leads. Natural products have been a useful source for the discovery of anticancer and anti-infective agents including antimalarial agents such as quinine. The artemisinins, derived from the sweet wormwood that was originally used in Chinese herbal medicines, have become a frontline treatment for drug-resistant malaria
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