Chlororesistoflavins A and B, Chlorinated Benzopyrene Antibiotics Produced by the Marine-Derived Actinomycete <i>Streptomyces</i> sp. Strain EG32
Min Cheol Kim, Zhifei Li, Reiko Cullum, Tadeusz F. Molinski, Mennat Allah G. Eid, Ali M. S. Hebishy, Ahmed Hassan Ibrahim Faraag, Ahmed E. Abdel Moneim, Mohamed S. Abdelfattah, William Fenical
Abstract
As part of a collaborative biomedical investigation of actinomycete bacteria isolated from sediments collected along the northern coast of Egypt (Mediterranean Sea), we explored the antibacterial metabolites from a bacterium identified as a Streptomyces sp., strain EG32. HPLC analysis and antibacterial testing against methicillin-resistant Staphylococcus aureus (MRSA) resulted in the identification of six compounds related to the resistoflavin and resistomycin class. Two of these metabolites were the chlorine-containing analogues chlororesistoflavins A (1) and B (2). The absolute configurations of the lone stereogenic center (C-11b) in these metabolites were assigned by analysis of their ECD spectra. Interestingly, the ECD spectrum of chlororesistoflavin A (1) shows a Cotton effect of the n−π* transition antipodal to that of the parent natural product, a consequence of 1,3-allylic strain induced by the adjacent bulky chlorine atom that distorts the coplanarity of the carbonyl group with the π-system. The chiroptical analysis thus resolves the paradox and uniformly aligns the configuration of all analogues as identical to that reported for natural resistoflavin. Chlororesistoflavins A (1) and B (2) exhibited antibacterial activity against MRSA with a minimum inhibitory concentration of 0.25 and 2.0 μg/mL, respectively.