Studies on Chemical Structure Modification and Structure?Activity Relationship of Derivatives of Gambogic Acid at C(39) |
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| Authors: | Hao‐Peng Sun Zong‐Liang Liu Xin Xue Yuan Gao Lei Zhang Jin‐Xin Wang Qing‐Long Guo Qi‐Dong You |
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| Institution: | 1. State Key Laboratory of Natural Medicines, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, P.?R. China, (phone/fax: +86‐25‐83271351);2. Key Laboratory of Carcinogenesis and Intervention of Jiangsu Province, China Pharmaceutical University, Nanjing 210009, P.?R. China |
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| 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. |
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| Keywords: | Gambogic acid derivatives Anticancer activity Structure?activity relationship (SAR) |
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