A New Antimycin Analog from Marine-Derived Streptomyces sp.

The American Cancer Society has reported that ovarian cancer is the leading cause of death among all other cancers of the female reproductive system. As approximately 20,000 women in the United States are afflicted with this disease each year, developing effective cancer therapies is essential. The Murphy Lab at UIC focuses on generating potential drug leads or molecular probes from novel biologically active secondary metabolites produced by aquatic-derived actinomycete bacteria.

Upon screening a library of actinomycete-derived fractions against ovarian cancer cell line OVCAR5, it was found that the secondary metabolites of strain A046 (Streptomyces sp., collected from Urrel Beach in Winthrop, Massachusetts) displayed submicromolar inhibitory activity (LD_{50 =} < 1.25 µg/mL). This strain was then cultured in 29 L of saltwater media and the extracellular metabolites were extracted. After several chromatographic steps, three metabolites of the antimycin class were isolated, two of which were identified as kitamycin A and N-formylantimycic acid methyl ester. Based on high resolution mass spectrometry and ¹H NMR analysis, we anticipate the third metabolite to be a novel antimycin analog- a class of molecules known to inhibit mitochondrial respiration. Herein, the isolation, structure elucidation, and biological activity of these metabolites will be discussed.