Anti-MRSA Dimeric and Brominated Phenyltetracenoids Produced by Streptomyces morookaense SC1169.

Eleven new phenyltetracenoid polyketides, streptovertimycins U ( 1 ) and V ( 2 ), 14-bromo-streptovertidione ( 3 ), streptovertimycins W-Y ( 4 - 6 ), and streptovertimycins Z 1 -Z 5 ( 7 - 11) , together with the known congeners fasamycins R ( 12 ) and S ( 13 ) and accramycins A ( 14 ) and B ( 15 ), were isolated from the NaBr-supplemented rice-grown cultures of Streptomyces morookaense SC1169. Their structures were elucidated by extensive spectroscopic analysis, single-crystal X-ray diffraction analysis, and theoretical computations of ECD spectra. Compounds 1 and 2 are methylene-bridged dimers of accramycin A, and compounds 3 and 7 - 11 are brominated fasamycin congeners. Compounds 5 and 8 - 14 exhibited activity against the drug-resistant bacteria MRSA and VRE (MIC = 0.6-5.0 μg/mL), and the dimer 1 displayed activity against MRSA (MIC = 2.5 μg/mL). Compounds 6 - 15 showed cytotoxicity against the human carcinoma A549, HeLa, HepG2, and MCF-7 cells in the IC 50 range between 1.7 and 9.2 μM.