Abstract

Discovery of new, inexpensive, and effective drugs is extremely urgent to combat malaria because most antimalarials have now become ineffective due to widespread drug resistance. Marine biodiversity is an enormous source of novel chemical entities and has been barely investigated for antimalarial drug discovery. In an effort to discover novel therapeutics for malaria, we studied the antimalarial activities of a unique marine macroorganism-derived peak fraction library developed by Harbor Branch Oceanographic Institute (HBOI). Our goal is to tap into the chemical and biological diversity of the HBOI peak library as a source of novel bioactive natural products. It is believed that the biological diversity from marine ecosystems is even higher than tropical rain forests and marine natural products have been shown to exhibit higher “hit-rates” than those of terrestrial plants. Within this unique library, we have screened 2,830 marine natural product (MNP) peak fractions through a medium throughput screening effort utilizing the SYBR Green-I fluorescence based assay, and have identified 253 fractions that exhibit antimalarial activity. From those inhibiting fractions we have identified twenty species of marine organisms that inhibit Plasmodium falciparum growth, from which thirty-five fractions were selected for further study. Among those thirty-five, eighty-three percent were also found to inhibit the chloroquine resistant P. falciparum strain, Dd2. The most potent inhibitors were then screened for their cytotoxic properties using the MTT cell viability assay. Bioassay guided fractionation using a Combiflash system is in progress to identify the active compounds from these fractions.