微波辅助高效合成2-氮杂环丁酮类衍生物及其抗肿瘤活性研究

Microwave-assisted facile synthesis of 2-azetidinone derivatives and evaluation of their antitumor activities

含氮杂环是非常重要的一类有机化合物,具有广泛的生物活性和药理活性,目前临床上正在使用或者处于研究开发的许多药物结构中都含有含氮杂环.因此,含氮杂环的快速高效合成及其生物活性研究一直都是有机化学和药物化学领域的研究热点之一.本文利用Ugi反应设计合成了两类具有潜在抗癌活性的2-氮杂环丁酮类衍生物,其结构均经核磁共振氢谱(~1H NMR)、碳谱(~13C NMR)和高分辨质谱(HRMS)确证.以人肺癌细胞A549、人胶质瘤细胞LN229、人乳腺癌细胞MDA-MB-453、人结肠癌细胞SW620和人前列腺癌细胞DU145等5种细胞株为活性筛选对象,采用噻唑蓝(MTT)法对目标分子进行了体外抗肿瘤活性研究,结果表明,所合成的目标分子具有一定的体外抗肿瘤活性,其中化合物7e和13e分别对LN229和DU145的抑制率达到了53%,具有可进一步深入研究的价值.

Nitrogen heterocyclic scaffold is one of very important derivatives in organic compounds, which possesses a wide range of biological activities and pharmacological activities and also has wide applications in many drugs, clinic trials and scientific researches. So, exploring fast and efficient synthetic methods of nitrogen heterocycles have been one of hot topics in organic chemistry. In this article, two series of 2-azetidinone analogues with potential antitumor activities were designed and synthesized via post-Ugi cascade reaction. The structures of the target molecules were characterized by 1H NMR, 13C NMR and HRMS spectra. The cancer cell lines LN229, MDA-MB-453, SW620, and DU145 were selected to evaluate the antitumor activity in vitro via MTT method. The results showed most compounds exhibited inhibitory activities against the cancer cells. Particularly, compounds 7e and 13e exhibited respectful antitumor activities in LN229 and DU145 cancer cell lines respectively with 53% inhibition, which are potential for further drug discovery.