基于三唑并噻二嗪骨架的新型抗肿瘤药物发现及体外药效评价

Discovery and In Vitro Efficacy Evaluation of Novel Anti-tumor Drugs Based on Triazolothiazide

为了探索三唑并噻二嗪骨架6位苯环上的取代基对其抗肿瘤活性的影响,本文基于课题组前期的研究基础,选取已报道的三唑并噻二嗪衍生物TR-33为先导结构,采用基于结构的药物优化策略,设计了8个三唑并噻二嗪骨架6位苯环取代衍生物。通过分子对接软件SYBYL7.3,以人体内微管蛋白为目标靶点进行药物筛选,获得了两个具有高潜能的小分子并予以化学合成,在体外抗肿瘤活性测试中发现两个小分子对人结肠癌细胞株(HT-29)有较好的抑制活性,此研究为后续该类小分子的设计与优化提供参考。

To explore the effect of substituents on the 6-position benzene ring of the triazolothiazide skeleton on its anti-tumor activity,based on the our previous research,selected the reported triazolothiazide derivative TR-33 as the lead compound,structure based drug optimization strategy adopted to design 10 triazolothiazide skeleton 6-position benzene ring substituted derivatives.Through the molecular docking software SYBYL 7.3,drug screening was carried out targeting human microtubule proteins,and two small molecules with high potential were obtained and chemically synthesized.In vitro anti-tumor activity showed that two compounds had good inhibitory activity on human colon cancer cell lines(HT-29).This study provides reference for the design and optimization of such structures in the future.