State Key Lab of Mycology, Institute of Microbiology, Chinese Academy of Sciences, No. 8 Beiertiao, Zhongguancun, Haidian District, Beijing 100190, PR China.
Bioorg Med Chem Lett. 2013 Jun 15;23(12):3547-50. doi: 10.1016/j.bmcl.2013.04.034. Epub 2013 Apr 22.
A new ophiobolin derivative, 3-anhydro-6-hydroxy-ophiobolin A (1), as well as two known ophiobolin derivatives 3-anhydro-ophiobolin A (2) and 3-anhydro-6-epi-ophiobolin A (3) were isolated from the PDB culture of a phytopathogenic fungus Bipolaris oryzae. The structure of 1 was elucidated through 2D NMR and other spectroscopic techniques. Compound 1 exhibited strong antimicrobial activity against Bacille Calmette-Guerin, Bacillus subtilis, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus with MIC value of 12.5 μg/mL, and potent antiproliferative activity against cell lines HepG2 and K562 with IC50 of 6.49 μM and 4.06 μM, respectively. Further studies on the cytotoxicity of compound 1 against K562 cells demonstrated that it induced apoptosis, observed by flow cytometric method. Preliminary structure-activity relationships of these ophiobolins and the mechanism of apoptosis induced by 1 were analyzed.
从植物病原菌稻丝核菌（Bipolaris oryzae）的 PDB 培养物中分离得到了一种新的蛇孢菌素衍生物 3-脱水-6-羟基蛇孢菌素 A（1），以及两种已知的蛇孢菌素衍生物 3-脱水蛇孢菌素 A（2）和 3-脱水-6-表蛇孢菌素 A（3）。通过 2D NMR 和其他光谱技术阐明了 1 的结构。化合物 1 对卡介苗、枯草芽孢杆菌、金黄色葡萄球菌和耐甲氧西林金黄色葡萄球菌具有很强的抗菌活性，MIC 值为 12.5 μg/mL，对 HepG2 和 K562 细胞系具有很强的抗增殖活性，IC50 值分别为 6.49 μM 和 4.06 μM。进一步研究化合物 1 对 K562 细胞的细胞毒性表明，它通过流式细胞术观察到诱导细胞凋亡。分析了这些蛇孢菌素的初步结构-活性关系以及 1 诱导细胞凋亡的机制。
