关键词: 白杨素, 衍生物, 甘氨酸, 抗肿瘤

Abstract:

In order to obtain novel lead compounds with high efficacy, low toxicity and minimum of side effects, using chrysin(5,7-dihydroxyflavone) with very broad biological activities as a starting material, four intermediates 7-O-carboxyalkylation chrysin derivatives(6—9) were synthesized by halogenation and hydrolysis. Four glycine methyl ester derivatives containing chrysin(12—15) were synthesized when the four intermediates above condensated with glycine methyl ester hydrochloride using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride(EDCI), N-hydroxybenzotriazole(HOBt) and 4-dimethylamiopryidine(DMAP) as a coupling reagent. And then the corresponding glycine derivatives of chrysin(16—19) were obtained by hydrolysis under conditions of room temperature and pH 10—11. The structures of the target compounds were assigned by ¹H NMR, ¹³C NMR, IR and MS. Taking cisplatin as a reference substance, the in vitro antitumor activity tests for target compounds against human hepatocellular carcinoma HepG2 cells and gastric carcinoma MGC-803 cells were carried out by MTT method. The results of primary pharmacological tests indicated that five compounds(14—16, 18, 19) possessed the more potent antitumor activity than chrysin in vitro. What’s more, the antitumor activity of compound 18(IC₅₀=4.36 μmol/L) against MGC-803 cells was better than the positive reference compound cisplatin(IC₅₀=4.40 μmol/L).

Key words: Chrysin, Derivative, Glycine, Antitumor activity