School of Marine Sciences, Sun Yat-sen University, Zhuhai 519000, China.
Southern Marine Sciences and Engineering Guangdong Laboratory (Zhuhai), Zhuhai 519000, China.
J Nat Prod. 2023 Dec 22;86(12):2651-2660. doi: 10.1021/acs.jnatprod.3c00664. Epub 2023 Nov 15.
Glioma is a clinically heterogeneous type of brain tumor with a poor prognosis. Current treatment approaches have limited effectiveness in treating glioma, highlighting the need for novel drugs. One approach is to explore marine natural products for their therapeutic potential. In this study, we isolated nine shikimate-derived diisoprenyl-cyclohexene/ane-type meroterpenoids (-), including four new ones, amphicordins A-D (-) from the ascidian-derived fungus SYSU-MS7908, and further semisynthesized four derivatives (-). Their structures were extensively characterized using 1D and 2D NMR, modified Mosher's method, HR-ESIMS, NMR and ECD calculations, and X-ray crystallography. Notably, amphicordin C () possesses a unique benzo[]chromene (6/6/6) skeleton in this meroterpenoid family. In an anti-glioma assay, oxirapentyn A () effectively inhibited the proliferation, migration, and invasion of glioma cells and induced their apoptosis. Furthermore, an analysis suggested that oxirapentyn A has the potential to penetrate the blood-brain barrier. These findings highlight the potential of oxirapentyn A as a candidate for the development of novel anti-glioma drugs.
神经胶质瘤是一种临床异质性的脑肿瘤，预后不良。目前的治疗方法在治疗神经胶质瘤方面效果有限，这凸显了开发新型药物的必要性。一种方法是探索海洋天然产物的治疗潜力。在这项研究中，我们从来源于棘皮动物的真菌 SYSU-MS7908 中分离得到了 9 种来源于莽草酸的双异戊烯基环己烯/烷型倍半萜类化合物（-），包括 4 个新化合物 amphicordins A-D（-），并进一步半合成了 4 个衍生物（-）。它们的结构通过 1D 和 2D NMR、改进的 Mosher 法、高分辨电喷雾电离质谱（HR-ESIMS）、NMR 和 ECD 计算以及 X 射线晶体学进行了广泛的表征。值得注意的是，在这个倍半萜类化合物家族中，amphicordin C（-）具有独特的苯并[ ]色烯（6/6/6）骨架。在抗神经胶质瘤测定中，oxirapentyn A（-）有效抑制神经胶质瘤细胞的增殖、迁移和侵袭，并诱导其凋亡。此外，分析表明 oxirapentyn A 有可能穿透血脑屏障。这些发现突显了 oxirapentyn A 作为新型抗神经胶质瘤药物开发的候选物的潜力。
