Zhang Yang, Zhang Zhuowei, Wang Bo, Liu Ling, Che Yongsheng
State Key Laboratory of Toxicology & Medical Countermeasures, Beijing Institute of Pharmacology & Toxicology, Beijing 100850, PR China.
State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, PR China.
Bioorg Med Chem Lett. 2016 Apr 15;26(8):1885-8. doi: 10.1016/j.bmcl.2016.03.022. Epub 2016 Mar 8.
Brasilamide E (1) is a bisabolane sesquiterpenoid isolated from the solid-substrate fermentation cultures of a plant endophytic fungus Paraconiothyrium brasiliense. The compound specifically inhibited proliferation of the MCF-7 cells, but did not show cytotoxicity towards the negative controls HaCaT and NIH3T3 cells (IC50>50 μM). To improve its potency while maintain selectivity, a total of 27 derivatives of 1 were designed, synthesized, and evaluated for in vitro cytotoxicity against six tumor cell lines and the negative control NIH3T3 cells. Among these compounds, compound 12b showed significantly improved potency against the MCF-7, HeLa, and HO8910 cells with IC50 values of 0.13-0.25 μM compared to 1 (IC50 8.47-18.00 μM), and remained nontoxic to the NIH3T3 cells.
巴西酰胺E（1）是一种从植物内生真菌巴西拟茎点霉的固体基质发酵培养物中分离得到的没药烷倍半萜。该化合物特异性抑制MCF-7细胞的增殖，但对阴性对照HaCaT和NIH3T3细胞未显示细胞毒性（IC50>50μM）。为了在保持选择性的同时提高其效力，共设计、合成了1的27种衍生物，并评估了它们对六种肿瘤细胞系和阴性对照NIH3T3细胞的体外细胞毒性。在这些化合物中，化合物12b对MCF-7、HeLa和HO8910细胞的效力显著提高，IC50值为0.13-0.25μM，而1的IC50值为8.47-18.00μM，并且对NIH3T3细胞仍无毒性。
