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Studies on Chemical Structure Modification and StructureActivity Relationship of Derivatives of Gambogic Acid at C(39)
Author(s) -
Sun HaoPeng,
Liu ZongLiang,
Xue Xin,
Gao Yuan,
Zhang Lei,
Wang JinXin,
Guo QingLong,
You QiDong
Publication year - 2012
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.201100415
Subject(s) - gambogic acid , chemistry , natural product , chemical structure , structure–activity relationship , stereochemistry , rational design , lead compound , chemical modification , potency , cancer cell lines , combinatorial chemistry , in vitro , cancer cell , biochemistry , organic chemistry , cancer , nanotechnology , medicine , materials science
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 structureactivity 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 structureactivity relationships (SARs) were discussed. The anti‐proliferation data were accquired through MTT (=3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2 H ‐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.