Chemistry & Biodiversity 2012-08-01

Studies on chemical structure modification and structure-activity relationship of derivatives of gambogic acid at C(39).

Hao-Peng Sun, Zong-Liang Liu, Xin Xue, Yuan Gao, Lei Zhang, Jin-Xin Wang, Qing-Long Guo, Qi-Dong You

Index: Chem. Biodivers. 9(8) , 1579-90, (2012)

Full Text: HTML

Abstract

The natural product gambogic acid exhibits high potency in inhibiting cancer cell lines. Rational medicinal modifications on gambogic acid will improve its physicochemical properties and drug-like characters. To investigate the structure-activity relationship of gambogic acid and also to find rational modification position on its chemical skeleton, we designed, synthesized, and characterized 16 derivatives of gambogic acid that were modified at C(39). The structure-activity relationships (SARs) were discussed. The anti-proliferation data were accquired through MTT (=3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assays of A549, BGC823, U251, HepG2, and MDA-MB-231 cancer cell lines. Most of the synthesized compounds showed strong inhibitory effects. The SAR study revealed that derivatives with aliphatic amino moieties at C(39) were more potent than those with other substituents. The C(39) position can undergo different kinds of chemical modifications without leading to loss of activity. Compounds 4 and 6 can serve as potential lead compounds for further development of new anticancer drugs.Copyright © 2012 Verlag Helvetica Chimica Acta AG, Zürich.

Related Compounds

  • Gambogic Acid

Related Articles:

Induction of programmed erythrocyte death by gambogic acid.

2012-01-01

[Cell Physiol. Biochem. 30(2) , 428-38, (2012)]

Gambogic acid as a non-competitive inhibitor of ATP-binding cassette transporter B1 reverses the multidrug resistance of human epithelial cancers by promoting ATP-binding cassette transporter B1 protein degradation.

2013-01-01

[Basic Clin Pharmacol Toxicol. 112(1) , 25-33, (2013)]

Subcellular localization and activity of gambogic acid.

2012-05-29

[ChemBioChem. 13(8) , 1191-8, (2012)]

Interaction between Gambogic acid and dihydrofolate reductase and synergistic lethal effects with methotrexate on hepatoma cells.

2013-01-01

[Anticancer Res. 33(1) , 133-42, (2013)]

Gambogic acid inhibits invasion of osteosarcoma via upregulation of TIMP-1.

2013-01-01

[Int. J. Mol. Med. 31(1) , 105-12, (2013)]

More Articles...