State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou 510070, China.
Program for Natural Products Chemical Biology, Key Laboratory of Plant Resources Conservation and Sustainable Utilization, Guangdong Provincial Key Laboratory of Applied Botany, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou 510650, China.
Fitoterapia. 2020 Nov;147:104768. doi: 10.1016/j.fitote.2020.104768. Epub 2020 Nov 7.
The chemical investigation of the secondary metabolites of Paramyrothecium roridum (homotypic synonym: Myrothecium roridum), an endophytic fungus isolated from the medicinal plant Morinda officinalis, led to the isolation of twelve cytotoxic trichothecene macrolides, including two new ones, named myrothecines H and I. The structures of the new macrolides were elucidated by extensive spectroscopic measurements analyses. In addition, the cytotoxic activities of these compounds were evaluated against SF-268, NCI-H460, and HepG-2 tumor cell lines, and all isolated compounds (1-12) exhibited significant cytotoxic activity with the IC ranging from 0.0002-16.2 μM. Moreover, the inhibitory activity of myrothecines H and I was evidenced by inducing phosphorylation of JNK (c-Jun N-terminal protein kinase) protein and the PARP (poly ADP-ribose polymerase) cleavage, and eventually induce apoptosis of HepG-2 cells. The results indicated that myrothecines H and I could be applied as chemotherapeutic agents.
内生真菌 Paramyrthecium roridum（同型同义词：Myrothecium roridum）是从药用植物桑黄中分离出来的，对其次级代谢产物的化学研究导致了 12 种细胞毒性的曲菌素大环内酯的分离，其中包括两种新化合物，命名为 myrothecines H 和 I。通过广泛的光谱测量分析确定了新大环内酯的结构。此外，还评估了这些化合物对 SF-268、NCI-H460 和 HepG-2 肿瘤细胞系的细胞毒性，所有分离得到的化合物（1-12）均表现出显著的细胞毒性，IC50 范围为 0.0002-16.2 μM。此外，myrothecines H 和 I 通过诱导 JNK（c-Jun N-末端蛋白激酶）蛋白的磷酸化和 PARP（多聚 ADP-核糖聚合酶）的切割，证实了其抑制活性，最终诱导 HepG-2 细胞凋亡。结果表明，myrothecines H 和 I 可作为化疗药物应用。
