School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan, Hubei 430074, PR China.
Org Biomol Chem. 2019 Aug 28;17(34):7985-7994. doi: 10.1039/c9ob01552c.
Eleven new cytochalasins, curtachalasins F-P (1-11), were isolated from the rice fermentation of endophytic fungus Xylaria cf. curta. Their structures were identified by extensive spectroscopic methods, X-ray diffraction, and quantum chemistry calculations. Curtachalasin P possesses a unique 5/6/6/7 fused ring system. In the bioactivity screening for curtachalasins F-P, A-C, and E (1-15), compounds 1, 3-6, 8-13, and 15 did not show obvious cytotoxicity against primary mouse splenocytes. Furthermore, the immunosuppressive assay against concanavalin A (ConA) induced T lymphocyte cell proliferation and lipopolysaccharide (LPS) induced B lymphocyte cell proliferation showed that compound 1 results in significant selective inhibition on B-cell proliferation (IC50 value of 2.42 μM) and compound 10 has selective inhibition on T-cell proliferation (IC50 value of 12.15 μM). These interesting immunosuppressive properties of this class of compounds provide new clues to fulfill the urgent demand for new immunosuppressive drugs.
从内生真菌 Xylaria cf. curta 的大米发酵中分离到 11 种新的细胞色素素 curtachalasins F-P（1-11）。通过广泛的光谱方法、X 射线衍射和量子化学计算确定了它们的结构。Curtachalasin P 具有独特的 5/6/6/7 稠合环系统。在 curtachalasins F-P、A-C 和 E（1-15）的生物活性筛选中，化合物 1、3-6、8-13 和 15 对原代小鼠脾细胞没有明显的细胞毒性。此外，对刀豆蛋白 A（ConA）诱导的 T 淋巴细胞增殖和脂多糖（LPS）诱导的 B 淋巴细胞增殖的免疫抑制测定表明，化合物 1 对 B 细胞增殖具有显著的选择性抑制作用（IC50 值为 2.42 μM），化合物 10 对 T 细胞增殖具有选择性抑制作用（IC50 值为 12.15 μM）。这类化合物的这些有趣的免疫抑制特性为满足对新型免疫抑制剂的迫切需求提供了新的线索。
