Aurora激酶抑制剂ZM447439的合成及生物活性研究

摘要

Objective To synthesize and evaluate the biological activity of aurora kinase inhibitor ZM447439. Methods With 4-hydroxy-3-methoxybenzoic acid as the starting material, ZM447439 was prepared via esterification, substitution, nitration, reduction and cyclization reaction. In addition, the entire target compounds were determined against cancer cell lines U937, K562, A549, LoVo and HT29 and were screened for Aurora A/B kinase inhibitory activity in vitro . Results The target compounds were identified by 1H-NMR, MS and IR, and the overall yield of this process was 34% . Conclusion The target compounds demonstrate significant cell lines and Aurora A/B kinase inhibitory activities.%目的 优化Aurora激酶抑制剂ZM447439的合成路线,并对其体外生物活性进行评价.方法 以4-羟基-3-甲氧基苯甲酸为起始原料,通过酯化、取代、硝化、还原、关环等反应合成ZM447439,涉及到的中间体及目标产物结构经1HNMR,MS及IR确证.以MTT法研究其体外抗肿瘤活性(U937,K562,A549,LoVo及HT29细胞株),同时评价其体外AuroraA/B激酶抑制活性.结果 合成了Aurora A/B激酶抑制剂ZM447439并进行相关生物活性研究.结论 新合成路线总收率约34％,目标化合物具有较好的Aurora A/B激酶活性及肿瘤细胞增殖抑制活性.