来自大戟属植物角状大戟的抗肿瘤12-脱氧佛波醇酯。

Anti-tumor 12-deoxyphorbol esters from Euphorbia cornigera.

作者信息

Baloch Imam Bakhsh, Baloch Musa Kaleem, Saqib Qazi Najam us

机构信息

Department of Chemistry, Gomal University, Dera Ismail Khan, Pakistan.

出版信息

Eur J Med Chem. 2008 Feb;43(2):274-81. doi: 10.1016/j.ejmech.2007.03.016. Epub 2007 Apr 5.

DOI:10.1016/j.ejmech.2007.03.016

PMID:17512094

Abstract

Nine (1-8 and 10) new and two (9 and 11) known compounds have been isolated from roots of Euphorbia cornigera Boiss. Their structure and relative stereochemistry were acquired through NMR ((1)H, (13)C, COSY-45, HOHAHA, HMQC, HMBC, NOE and HMBC) spectroscopic measurements. Compounds 1-10 were identified as diesters of 13,20-O-diacyl and 11 as 13-O-acetyl of 12-deoxyphorbol. Cytotoxic activity of the compounds was investigated on human KB cells by reduction of MTT. Compounds 8-10 displayed IC(50) of 0.8, 0.5, and 1.0 microg mL(-1), respectively, whereas the activity of rest of the compounds (1-7) was either very low or (11) zero even up to 1000 microg mL(-1). The inhibition of DNA synthesis through Trypan blue exclusion and Brd-U assay was investigation to figure out the role of compounds 8-10 and concluded that these were responsible for the death of KB cells. Significant correlation has been found between the cytotoxicity and DNA cross-link and DNA strand-break formation.

摘要

从大戟科植物角状大戟（Euphorbia cornigera Boiss.）的根中分离出了9种（1 - 8和10）新化合物和2种（9和11）已知化合物。通过核磁共振（（1）H、（13）C、COSY - 45、HOHAHA、HMQC、HMBC、NOE和HMBC）光谱测量确定了它们的结构和相对立体化学。化合物1 - 10被鉴定为13,20 - O - 二酰基酯，化合物11被鉴定为12 - 脱氧佛波醇的13 - O - 乙酰基酯。通过MTT还原法研究了这些化合物对人KB细胞的细胞毒性活性。化合物8 - 10的IC（50）分别为0.8、0.5和1.0微克/毫升，而其余化合物（1 - 7）的活性非常低，甚至化合物11在高达1000微克/毫升时活性为零。通过台盼蓝排斥法和Brd - U测定法研究了对DNA合成的抑制作用，以确定化合物8 - 10的作用，并得出结论，这些化合物导致了KB细胞的死亡。已发现细胞毒性与DNA交联和DNA链断裂形成之间存在显著相关性。