2. Academic Validation
  3. Design and synthesis of gambogic acid analogs as potent cytotoxic and anti-inflammatory agents

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

  • Bioorg Med Chem Lett. 2012 Jun 15;22(12):4018-22. doi: 10.1016/j.bmcl.2012.04.084.
Chiao-Ting Yen 1,  Kyoko Nakagawa-Goto,  Tsong-Long Hwang,  Susan L Morris-Natschke,  Kenneth F Bastow,  Yang-Chang Wu,  Kuo-Hsiung Lee
Affiliations

Affiliation

  • 1 Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, NC 27599-7568, USA.
PMID: 22595179 DOI: 10.1016/j.bmcl.2012.04.084
Abstract

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 IC(50) values of 0.9 and 0.8 μg/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.

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