Design and synthesis of gambogic acid analogs as potent cytotoxic and anti-inflammatory agents

被引：32

作者：

Yen, Chiao-Ting ^{[2
,3
]}

Nakagawa-Goto, Kyoko ^{[2
]}

Hwang, Tsong-Long ^{[4
]}

Morris-Natschke, Susan L. ^{[2
]}

Bastow, Kenneth F. ^{[5
]}

Wu, Yang-Chang ^{[1
,6
,7
]}

Lee, Kuo-Hsiung ^{[2
,8
]}

机构：

[1] China Med Univ Hosp, Ctr Mol Med, Taichung 40447, Taiwan

[2] Univ N Carolina, UNC Eshelman Sch Pharm, Nat Prod Res Labs, Chapel Hill, NC 27599 USA

[3] Kaohsiung Med Univ, Grad Inst Nat Prod, Kaohsiung 807, Taiwan

[4] Chang Gung Univ, Grad Inst Nat Prod, Tao Yuan 333, Taiwan

[5] Univ N Carolina, UNC Eshelman Sch Pharm, Div Chem Biol & Med Chem, Chapel Hill, NC 27599 USA

[6] China Med Univ Hosp, Nat Med Prod Res Ctr, Taichung 40447, Taiwan

[7] China Med Univ, Sch Chinese Med, Coll Chinese Med, Taichung 40402, Taiwan

[8] China Med Univ & Hosp, Chinese Med Res & Dev Ctr, Taichung 40447, Taiwan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 12期

关键词：

1,3,6-Trihydroxy-9H-xanthen-9-one; Ggambogic acid (GA); Prenylxanthones; Pyranoxanthones; Cytotoxicity; Anti-inflammatory activity; CELL-LINES; GAMMA-MANGOSTIN; IN-VITRO; XANTHONES; INHIBITION; GROWTH; PROTEIN; CONSTITUTION; DERIVATIVES; SUPEROXIDE;

D O I：

10.1016/j.bmcl.2012.04.084

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Prenyl-and pyrano-xanthones derived from 1,3,6-trihydroxy-9H-xanthen-9-one, a basic backbone of gambogic acid (GA), were synthesized and evaluated for in vitro cytotoxic effects against four human cancer cell lines (KB, KBvin, A549, and DU-145) and anti-inflammatory activity toward superoxide anion generation and elastase release by human neutrophils in response to fMLP/CB. Among them, prenylxanthones 7-13 were generally less active than pyranoxanthones 14-21 in both anticancer and anti-inflammatory assays. Furthermore, two angular 3,3-dimethypyranoxanthones (16 and 20) showed the greatest and selective activity against the KBvin multidrug resistant (MDR) cell line with IC50 values of 0.9 and 0.8 mu g/mL, respectively. An angular 3-methyl-3-prenylpyranoxanthone (17) selectively inhibited elastase release with 200 times more potency than phenylmethylsulfonyl fluoride (PMSF), the positive control. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：4018 / 4022

页数：5

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