Anti-MRSA Dimeric and Brominated Phenyltetracenoids Produced by <i>Streptomyces</i> <i>morookaense</i> SC1169
Xiaoxia Li, Ping Wu, Wanfang Wang, Jinghua Xue, Hanxiang Li, Haibo Tan, Xiaoyi Wei
Abstract
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.