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

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.

New Antimicrobial Accramycins from Streptomyces sp. MA37 Variant

“…Compound 1 showed the most significant antimicrobial activity against S. aureus DSM 2569 with the MIC at 0.81 µg/mL. This bioactivity was comparable to the positive control chloramphenicol with the MICs at 0.5 µg/mL (Table 1), and also consistent with the previous findings that depicted naphthacene-derived compounds, including fasamycins, nephthacemycins, formicamycins, and accramycins, to possess considerable antimicrobial bioactivity [2][3][4][5][6][7][8][9][10][11][12][13][14][15]. The presence of methoxy groups in C-28 and C-29 of 1 was likely responsible for the significant activity displayed in 1 which exhibited 6-fold and 12-fold inhibitions over 2 and 3, respectively.…”

“…Naphthacemycins are aromatic polyketides derived from the type II polyketide biosynthetic pathways [1]. The backbone structure of this group of microbial natural products is composed of a partly reduced 1-phenyltetracene moiety (Figure 1) [2][3][4][5][6][7][8][9][10][11][12][13][14][15]. Due to their innate and potent antimicrobial activities, this group of polyketides has attracted the interest of medicinal chemists worldwide to study the structure-activity relationships of the different groups, especially the fasamycins [16][17][18].…”