Planta Med 2013; 79 - CL12
DOI: 10.1055/s-0033-1348537

Structure Elucidation and Therapeutic Potential of Three Novel Classes of Natural Products from an Dscidian-Derived Actinomadura sp.

TP Wyche 1, Y Hou 1, E Vazquez-Rivera 1, D Braun 1, WM Westler 2, DR Andes 3, TS Bugni 1
  • 1Division of Pharmaceutical Sciences, University of Wisconsin-Madison, 777 Highland Avenue, Madison, WI 53705, USA
  • 2Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706
  • 3School of Medicine, University of Wisconsin-Madison, Madison, WI 53705

Principal component analysis (PCA) of LCMS data, obtained from a collection of bacterial strains, was used to identify unique chemistry from a marine Actinomadura sp. isolated from the ascidian Ecteinascidia turbinata. The Actinomadura sp. was found to produce three novel classes of compounds. The structures were determined by NMR and MS, including a 13C-13C COSY of isotopically enriched compounds. Importantly, the novel compounds demonstrated therapeutic potential: halomadurones A-D demonstrated potent Nrf2-ARE activity, forazoline A demonstrated in vivo efficacy in a mouse model of Candida albicans, and ecteinamycin had a minimum inhibitory concentration (MIC) of 0.125 µg/mL against methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA).