Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, China.
Sci Rep. 2017 Feb 13;7:42434. doi: 10.1038/srep42434.
Two new tetracyclic cytochalasans, flavichalasines A and B (1 and 2), three new pentacyclic cytochalasans, flavichalasines C-E (3-5), and eight new tricyclic cytochalasans, flavichalasines F-M (6-13), together with eight known analogues (14-21), were isolated from the solid culture of Aspergillus flavipes. Structures of these new compounds were elucidated on the basis of extensive spectroscopic analyses including 1D, 2D NMR and HRESIMS data. Their absolute configurations were determined by comparison of their experimental ECD with either computed ECD or experimental ECD spectrum of known compound. The structure and absolute configuration of 2 were further determined by X-ray crystallographic diffraction. Flavichalasine A (1) represents the first example of cytochalasan with a terminal double bond at the macrocyclic ring and flavichalasine E (5) is the only cytochalasan with an α-oriented oxygen-bridge in D ring. These new compounds were evaluated for their cytotoxic activities against seven human cancer cell lines, of which, 6 and 14 displayed moderate inhibitory activities against tested cell lines. In addition, compounds 6 and 14 induced apoptosis of HL60 cells by activation of caspase-3 and degradation of PARP.
从黄曲霉的固体培养物中分离得到两种新的四环细胞松弛素，即 flavichalasines A 和 B（1 和 2），三种新的五环细胞松弛素，即 flavichalasines C-E（3-5），以及八种新的三环细胞松弛素，即 flavichalasines F-M（6-13），此外还有八种已知类似物（14-21）。这些新化合物的结构是根据广泛的光谱分析确定的，包括 1D、2D NMR 和 HRESIMS 数据。通过将实验 ECD 与已知化合物的计算 ECD 或实验 ECD 光谱进行比较，确定了它们的绝对构型。通过 X 射线晶体学衍射进一步确定了 flavichalasine A（1）的结构和绝对构型。flavichalasine A（1）是第一个具有大环中环末端双键的细胞松弛素，而 flavichalasine E（5）是唯一一个在 D 环中具有α-取向氧桥的细胞松弛素。这些新化合物对七种人癌细胞系进行了细胞毒性活性评价，其中 6 和 14 对测试细胞系显示出中等抑制活性。此外，化合物 6 和 14 通过激活 caspase-3 和 PARP 的降解诱导 HL60 细胞凋亡。
