木犀草素硝酸酯衍生物的合成及其体外活性研究

目的 设计合成新型硝酸酯类木犀草素衍生物.方法 采用在木犀草素母核C-3′和C-4′之间插入醚键,再在C7-OH上进行亲核取代,合成了5个目标化合物,结构经IR、NMR等确证;采用Griess方法测定目标化合物的体外NO释放情况,并通过MTT方法初步测定抗肿瘤活性.结果 在所合成的化合物中,化合物3a与3b的NO释放较迅速,且很快就到达平衡;同时,6a～6c系列化合物NO释放平稳,表明对木犀草素邻二酚羟基不同保护结构的修饰,影响了NO的体外释放;5个目标化合物对人肝癌细胞HepG-2和人乳腺癌细胞MCF-7无明显细胞毒性.结论 硝酸酯类木犀草素衍生物的NO释放量与抗肿瘤活性无相关性,合理的修饰有利于提高活性.

Synthesis and in vitro activities studies of luteolin nitrate derivatives

Objective To design and synthesize new nitrates of luteolin. Methods Five target compounds were obtained by inserting an ether linkage between C-3′, C-4′of luteolin, then the C7-OH of luteolin was replaced by nitrate via nucleophilic substitution. IR and NMR were used for the structural characterization. NO release of the compounds in vitro was determined by Griess method, and the antitumor activity was measured by MTT method. Results The NO release of compounds 3a and 3b were quick and reached equilibrium rapidly and the release of 6a-6c series compounds were stable. The results showed that the protective structure of luteolin at the two phenolic hydroxyl groups affected the NO release in vitro. The MTT results showed the series of new compounds are non-toxic against HepG-2 and MCF-7 human cancer cell lines. Conclusion There is no correlation between the release of the nitric oxide and anti-tumor activity of luteolin nitrates. The activity could be improved by reasonable modification.