Atropisomeric Dihydroanthracenones as Inhibitors of Multiresistant Staphylococcus aureus
Atropisomeric Dihydroanthracenones as Inhibitors of Multiresistant Staphylococcus aureus
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DOI：
10.1021/jm301816a
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发表时间：
2013-04-25
影响因子：
7.3
通讯作者：
Proksch, Peter
中科院分区：
文献类型：
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作者：
Bara, Robert;Zerfass, Ilka;Proksch, Peter
从芦荟内生菌Talaromyceswortmannii中分离得到两个双二氢蒽酮对映体，包括同二聚体黄甘露醇A（1）和以前未报道的黄甘露醇B（2），两个新的不对称二聚体（3和4），以及两个新的混合二氢蒽酮/蒽醌二聚体（5和6）。2-6的结构通过广泛的NMR和质谱分析来阐明。联芳基的轴向手性使用TDDFT ECD和VCD计算确定，然而，其组合不允许分配的中心手性元素1。该化合物对金黄色葡萄球菌，包括（多）耐药临床分离株表现出抗菌活性。报告基因分析表明诱导SOS反应的一些衍生物，这表明干扰DNA结构或代谢。荧光显微镜显示细菌染色体分离缺陷和DNA降解。值得注意的是，这些化合物没有显示出细胞毒性活性，这鼓励了它们作为抗菌药物开发的潜在起点的进一步评价。
Two bisdihydroanthracenone atropodiastereomeric pairs, including homodimeric flavomannin A (1) and the previously unreported flavomannin B (2), two new unsymmetrical dimers (3 and 4), and two new mixed dihydroanthracenone/anthraquinone dimers (5 and 6) were isolated from Talaromyces wortmannii, an endophyte of Aloe vera. The structures of 2-6 were elucidated by extensive NMR and mass spectrometric analyses. The axial chirality of the biaryls was determined using TDDFT ECD and VCD calculations, the combination of which however did not allow the assignment of the central chirality elements of 1. The compounds exhibited antibacterial activity against Staphylococcus aureus, including (multi)drug-resistant clinical isolates. Reporter gene analyses indicated induction of the SOS response for some of the derivatives, suggesting interference with DNA structure or metabolism. Fluorescence microscopy demonstrated defective segregation of the bacterial chromosome and DNA degradation. Notably, the compounds showed no cytotoxic activity, encouraging their further evaluation as potential starting points for antibacterial drug development.