具有醚侧链的新型佛波醇衍生物的合成及其抗HIV活性评估。

Synthesis of new phorbol derivatives having ethereal side chain and evaluation of their anti-HIV activity.

作者信息

Matsuya Yuji, Yu Zhong, Yamamoto Naoki, Mori Masao, Saito Haruo, Takeuchi Makoto, Ito Mamiko, Nemoto Hideo

机构信息

Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0914, Japan.

出版信息

Bioorg Med Chem. 2005 Jul 15;13(14):4383-8. doi: 10.1016/j.bmc.2005.04.056.

DOI:10.1016/j.bmc.2005.04.056

PMID:15908223

Abstract

Several new phorbol derivatives having ethereal substituents at the 12-position were synthesized and subjected to biological evaluation to find new candidates of an anti-HIV agent. Among them, 12-O-(methoxymethyl)phorbol 13-decanoate showed potent inhibitory activity against infection of HIV-1 in MT-4 cells (EC50: 1.3 ng/mL) and relatively low cytotoxicity (CC50: 8.3 microg/mL). This compound was also found to have sufficient stability in mouse plasma compared with the corresponding 12-acetate derivative, which was an equipotent HIV-1 inhibitor, but with an activity that decreased considerably after plasma treatment.

摘要

合成了几种在12位带有醚取代基的新型佛波醇衍生物，并对其进行生物学评价以寻找抗HIV药物的新候选物。其中，12-O-(甲氧基甲基)佛波醇13-癸酸酯对MT-4细胞中HIV-1感染表现出强效抑制活性(EC50: 1.3 ng/mL)且细胞毒性相对较低(CC50: 8.3 μg/mL)。还发现该化合物与相应的12-乙酸酯衍生物相比在小鼠血浆中具有足够的稳定性，后者是一种等效的HIV-1抑制剂，但经血浆处理后活性大幅下降。