Institut für Pharmazeutische Biologie und Biotechnologie, Heinrich-Heine-Universität Düsseldorf, Universitätsstrasse 1, Geb. 26.23, 40225 Düsseldorf, Germany.
J Med Chem. 2013 Apr 25;56(8):3257-72. doi: 10.1021/jm301816a. Epub 2013 Apr 16.
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.
从库拉索芦荟内生真菌塔宾曲霉菌中分离得到了两个双二氢蒽酮对映二聚体，包括同二聚体 flavomannin A（1）和以前未报道的 flavomannin 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）。通过广泛的 NMR 和质谱分析确定了 2-6 的结构。使用 TDDFT ECD 和 VCD 计算确定了联芳烃的轴向手性，但组合起来无法确定 1 的中心手性元素。这些化合物对金黄色葡萄球菌表现出抗菌活性，包括（多）药耐药的临床分离株。报告基因分析表明，一些衍生物诱导 SOS 反应，表明它们干扰了 DNA 结构或代谢。荧光显微镜显示细菌染色体的分离缺陷和 DNA 降解。值得注意的是，这些化合物没有细胞毒性活性，这鼓励进一步评估它们作为潜在的抗菌药物开发的起点。
