Discovery of antimicrobial compounds from Lendenfeldia, Ircinia and Dysidea sponges using bioassay guided fractionation of marine extracts

Abstract

ABSTRACTMultidrug resistant bacteria have emerged as a threat to public health all over the world. At the same time, the discovery of new bioactive small molecules with antimicrobial activity and suitable pharmacological properties has waned. Herein we report the screening of marine extracts to identify novel compounds with antimicrobial activity. Bioassay guided fractionation has enabled the discovery and identification of a family of simple amines with promising activity against methicillin resistant Staphylococcus aureus (MRSA). To confirm the natural product structures proposed, these compounds and analogues have been prepared synthetically. Several of the synthetic analogues showed promising bioactivity against the medically important pathogens MRSA (MICs to 12.5 µM), Mycobacterium tuberculosis (MICs to 0.02 µM), uropathogenic Escherichia coli (MIC 6.2 µM) and Pseudomonas aeruginosa (MIC 3.1 µM). Cross-referencing antimicrobial activity and toxicity show that these synthetic compounds display a favourable therapeutic index for their target pathogens.