Design,Synthesis,and Anticancer Activity Of Gambogenic Acid Derivatives

Gambogenic acid (GNA) is one of the major active ingredients of gamboge. Theresult has shown that due to its strong anti-tumor activity, broad anti-tumor spectrumand less toxic, the GNA has good curative effect on liver cancer, gastric cancer,nasopharyngeal carcinoma and adenocarcinoma of the lung. Furthermore, because GNAis selective for tumor cells and has less impact on the hematopoietic system and theimmune function in normal animals, it is a natural anti-cancer drug with greatdevelopment prospects. However, the clinical use of GNA was limited due to its poorwater-solubility （<1mg/ml）.As a result, this paper focuses on the structural modification of GNA. On the basisof maintaining the main structure of GNA, we modified the carboxyl group on C-29position by esterification or amidation reaction. Different amines were introduced inorder to obtain target compounds with better water-solubility and higher anti-tumoractivity. This paper consists of four parts:Part one: IntroductionThe paper introduces the research status of gamboge and structure transformation ofgambogic acid.Part two: Design, synthesis of gambogenic acid derivatives1. Technological optimization of GNA preparation2. Design, synthesis of amino esters of GNAWe took gambogenic acid as a leading compound, twelve novel amino estersderivatives of GNA were designed and synthesized, the structures of target compoundswere determined by IR,1H NMR, MS. 3. Design, synthesis of gambogenic acid amidesBase on C-29carboxyl unit of GNA, four novel amino esters derivatives of GNAwere designed and synthesized by structure modification, which introduction ofdifferent nitrogen-containing group, such as morpholine, piperidine, diethylamine andimidazole. The structures of target compounds were determined by IR,1H NMR, MS.Part three: Preliminary study on antitumor activity in vitroTheir antitumor activities were evaluated in vitro by MTT assay.Part four: ConclusionIn conclusion, sixteen target compounds were synthesized by structuremodification. Based on our preliminary results，these compounds have potent antitumoractivity.