Versixanthones A-F, Cytotoxic Xanthone-Chromanone Dimers from the Marine-Derived Fungus Aspergillus versicolor HDN1009
Versixanthones A-F, Cytotoxic Xanthone-Chromanone Dimers from the Marine-Derived Fungus Aspergillus versicolor HDN1009
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DOI：
10.1021/acs.jnatprod.5b00636
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发表时间：
2015-11-01
影响因子：
5.1
通讯作者：
Li, Dehai
中科院分区：
文献类型：
--
作者：
Wu, Guangwei;Yu, Guihong;Li, Dehai
从红木曲霉（Aspergillus versicolor） HDN1009培养中分离出6种不同的四羟基蒽酮和2,2-二取代的4- 1- 1单体形式键的异色蒽酮二聚体（versixanthones a - f(1-6)）。通过x射线衍射分析、化学转化和TDDFT-ECD计算，确定了1-6的绝对构型，代表了中心和轴向手性元素或首选螺旋度。在DMSO中，1和4之间以及2和3之间的不同联芳键通过逆oxa- michael机制相互转化，提供了对口蒽酮-铬罗曼酮二聚体形成的深入了解，并支持了它们绝对构型的分配。化合物1 ~ 6对7种肿瘤细胞系均表现出细胞毒性，其中IC50值最高为0.7 μ M.化合物5对拓扑异构酶I有进一步的抑制作用。
Six unusual xanthone-chromanone dimers, versixanthones A-F (1-6), featuring different formal linkages of tetrahydroxanthone and 2,2-disubstituted chroman-4-one monomers, were isolated from a culture of the mangrove-derived fungus Aspergillus versicolor HDN1009. The absolute configurations of 1-6, representing the central and axial chirality elements or preferred helicities, were established by a combination of X-ray diffraction analysis, chemical conversions, and TDDFT-ECD calculations. The interconversion of different biaryl linkages between 1 and 4 and between 2 and 3 in DMSO by a retro-oxa-Michael mechanism provided insight into the formation of the xanthone-chromanone dimers and supported the assignments of their absolute configurations. Compounds 1-6 exhibited cytotoxicities against the seven tested cancer cell lines, with the best IC50 value of 0.7 mu M. Compound 5 showed further inhibitory activity against topoisomerase I.