Antitumor agents.: Part 209:: Pheophorbide-a derivatives as photo-independent cytotoxic agents

被引：50

作者：

Wongsinkongman, P ^{[1
]}

Brossi, A ^{[1
]}

Wang, HK ^{[1
]}

Bastow, KF ^{[1
]}

Lee, KH ^{[1
]}

机构：

[1] Univ N Carolina, Sch Pharm, Nat Prod Lab, Chapel Hill, NC 27599 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2002年 / 10卷 / 03期

关键词：

D O I：

10.1016/S0968-0896(01)00305-4

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

A methanotic crude extract of the plant Garuga pinnata Roxb. (Burseraceae) showed promising cytotoxic activity against a panel of human tumor cell lines in vitro. including KB and its drug-resistant sublines (Ferguson et al. Cancer Res. 1988, 48, 5956). Pheophorbide-a and-h methyl esters (3.4) were isolated as active principles with broad photo-dependent cytotoxic activities in the micromolar range. These findings prompted SAR studies of known and novel pheophorbide-a derivatives as photo-dependent and hoto-independent cytotoxic agents. The results showed that zinc-protoporphyrin IX (10). zinc 13(2)(R)-hydroxypheophorbide-a methyl ester (22), and zinc chlorin-e6 trimethyl ester (13) possessed photo-independent cytotoxic activity. Compounds 13 and 22 were the most active cytotoxic agents of the series (mean ED50 4.6 +/- 1.0 muM and 5.7 +/- 0.7 muM, respectively) against KB cells incubated in the dark. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：583 / 591

页数：9

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