高良姜素含氮衍生物的合成及其抗肿瘤活性

摘要

Galangin,a naturally occurring bioflavonoid,has a variety of pharmacological effects.However,few literatures on its structural modification have been reported.In the present study,five nitrogen-containing galangin derivatives were designed and synthesized,the structures of the synthesized derivatives were characterized by 1H NMR,13C NMR and MS,then the antitumor activities of these derivatives were assayed by MTT method.The results showed that the anti-proliferative activity against human prostatic carcinoma cell line PC-3 of 2-phenyl-3,5,7-trihydroxy-8-(morpholinomethyl)-4H-chromen-4-one 2c (IC50 11.37 μmol/L) and 2-phenyl-3,5,7-trihydroxy-8-(piperazin-1-ylmethyl)-4H-chromen-4-one 2d (IC50:13.57 μmol/L) were more potent than galangin (IC50:41.66 μmol/L) while the compound 2d exhibited the highest anti-proliferative activity against human colon cancer cell line Lovo with about 5.22-fold more potent than galangin.The increase of the antitumor activities of these derivatives was possibly related to the introduction of N-containing heterocyclic ring into the 8-site of galangin.%高良姜素是一种天然来源的黄酮醇类化合物,药理作用广泛,但尚未有关于其结构修饰的研究报道.本文以高良姜素为原料,设计、合成了5个高良姜素含氮衍生物,并对其结构进行1H NMR、13C NMR及MS表征;然后采用MTT法测试结构修饰产物的抗肿瘤活性,结果表明化合物2-苯基-3,5,7-三羟基-8-(吗啉甲基)-4H-色烯-4-酮(2c)和2-苯基-3,5,7-三羟基-8-(哌嗪-1-甲基)-4H-色烯-4-酮(2d)对人前列腺癌PC-3细胞株的增殖抑制活性(IC50:11.37和13.57 μmol/L)显著优于高良姜素(IC50:41.66 μmol/L),分别提高了3.66倍和3.07倍;化合物2-苯基-3,5,7-三羟基-8-(哌嗪-1-甲基)-4H-色烯-4-酮(2d)对人结肠癌LOVO细胞株的增殖抑制活性较高良姜素提高了5.22倍.该系列衍生物的抗肿瘤活性的增强可能与8-位上含氮杂环的引入有关.