Anti-MRSA Dimeric and Brominated Phenyltetracenoids Produced by Streptomycesmorookaense SC1169

Eleven new phenyltetracenoid polyketides, streptovertimycins U (1) and V (2), 14-bromo-streptovertidione (3), streptovertimycins W-Y (4-6), and streptovertimycins Z₁-Z₅ (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 IC₅₀ range between 1.7 and 9.2 μM.