HSQC-TOCSY Fingerprinting-Directed Discovery of Antiplasmodial Polyketides from the Marine Ascidian-Derived Streptomyces sp. (USC-16018)

Abstract

Chemical investigations on the fermentation extract obtained from an ascidian-derived <i>Streptomyces</i> sp. (USC-16018) yielded a new ansamycin polyketide, herbimycin G (<b>1</b>), as well as a known macrocyclic polyketide, elaiophylin (<b>2</b>), and four known diketopiperazines (<b>3</b>⁻<b>6</b>). The structures of the compounds were elucidated based on 1D/2D NMR and MS data. The absolute configuration of <b>1</b> was established by comparison of experimental and predicted electronic circular dichroism (ECD) data. Antiplasmodial activities were tested for the natural products against chloroquine sensitive (3D7) and chloroquine resistant (Dd2) <i>Plasmodium falciparum</i> strains; the two polyketides (<b>1</b>⁻<b>2</b>) demonstrated an inhibition of >75% against both parasite strains and while <b>2</b> was highly cytotoxic, herbimycin G (<b>1</b>) showed no cytotoxicity and good predicted water solubility.