Program in Biotechnology, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
J Nat Prod. 2011 Oct 28;74(10):2290-4. doi: 10.1021/np200491g. Epub 2011 Sep 28.
As part of our ongoing efforts to investigate natural products with potential for use as cancer treatments, we have recently disclosed the cytotoxicity of unique nor-chamigrane (1) and chamigrane (2, 3) endoperoxides from a Thai mangrove-derived fungus. Reinvestigation of this fungus in a large-scale fermentation led to the isolation of an additional new chamigrane endoperoxide (4) and one known analogue (5). Among these isolated metabolites, compound 3 (merulin C) exhibited potent antiangiogenic activity mainly by suppression of endothelial cell proliferation and migration in a dose-dependent manner, and its effect is mediated by reduction in the phosphorylation of Erk1/2. Merulin C also displayed promising activity in a rat aortic ring sprouting (ex vivo) and a mouse Matrigel (in vivo) assay.
作为我们正在进行的研究工作的一部分，旨在寻找具有癌症治疗潜力的天然产物，我们最近披露了一种来自泰国红树林来源的真菌的独特的 nor-chamigrane（1）和 chamigrane（2、3）内过氧化物的细胞毒性。对这种真菌进行大规模发酵的再研究导致分离出另一种新的 chamigrane 内过氧化物（4）和一种已知类似物（5）。在这些分离出的代谢物中，化合物 3（merulin C）表现出很强的抗血管生成活性，主要通过抑制内皮细胞增殖和迁移，呈剂量依赖性，其作用是通过减少 Erk1/2 的磷酸化来介导的。Merulin C 在大鼠主动脉环发芽（离体）和小鼠 Matrigel（体内）试验中也表现出有希望的活性。
