手性螺环氧化吲哚类化合物的设计、合成及抗肿瘤活性研究

Design,Synthesis,and Antitumor Activities of Chiral Spirooxindole Compounds

前期利用[2+1]环化反应合成了一系列手性螺环氧化吲哚类化合物,研究采用MTT法对这些化合物在结肠癌细胞CT26和宫颈癌细胞Hela中的抗肿瘤活性进行了评价,探析其构效关系,并在苗头化合物的基础上进行了结构优化设计合成了目标化合物,并再次评价其抗肿瘤效果。结果显示,27个手性螺环氧化吲哚-环丙烷-茚二酮类化合物对CT26和Hela细胞均具有良好的抗增殖作用。其中,16个化合物对CT26细胞的抑制活性优于阳性对照顺铂,14个化合物对Hela细胞的抗增殖能力与顺铂相当或更优。进一步,结构优化得到的化合物均能有效抑制CT26和Hela细胞的增殖,部分手性螺环氧化吲哚类目标化合物可作为抗肿瘤药物候选先导化合物,具有较好的研发潜力。

In the early stage,a series of chiral spirooxindole compounds were synthesized using[2+1]cyclization reaction.In this paper,the MTT method was used to evaluate the antitumor activity of these compounds on colon cancer cell CT26 and cervical cancer cell Hela,analyzing their structure-activity relationships.Subsequently,structural optimization based on promising compounds led to the synthesis of target compounds,followed by a reevaluation of their anti-tumor effects.The results demonstrated that all 27 chiral spirocyclic oxindole-cyclopropane-naphthyl-2-one compounds exhibited significant anti-proliferative effects on both CT26 and Hela cells.Among them,16 compounds showed higher inhibitory activity on CT26 cells compared to the positive control cisplatin,while 14 compounds exhibited anti-proliferative capabilities in Hela cells comparable to or better than cisplatin.Furthermore,the compounds obtained from structural optimization can effectively inhibit the proliferation of CT26 and Hela cells,and some chiral spirooxindole target compounds could be served as candidate lead compounds for antitumor drugs,with good research and development potential.