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Src与iNOS为肿瘤发生、转移中位于不同通路的重要靶酶,本文采用分子拼合的药物设计原理,设计合成了全新的酪氨酸Src蛋白激酶与iNOS的双重抑制剂。所设计合成的化合物经过Src激酶和iNOS的抑制活性检测及体外抗肿瘤测试,实验结果表明大部分化合物对于两种靶酶均表现出一定的抑制活性,部分化合物对于多种肿瘤细胞的增殖有一定的抑制作用。其中化合物33对Src激酶和iNOS均有比较好的抑制活性,对于肝癌HepG2和结肠癌HT-29细胞的增殖也有明显的抑制作用。
Src and iNOS are important target enzymes in different pathways of tumorigenesis and metastasis. In this paper, we designed and synthesized a new dual inhibitor of tyrosine Src protein kinase and iNOS using the molecular design principle of drug combination. The designed and synthesized compounds were tested for inhibitory activity of Src kinase and iNOS and anti-tumor in vitro. The experimental results showed that most of the compounds showed some inhibitory activity against both of the target enzymes and some of the compounds had certain proliferation on a variety of tumor cells Inhibition. Among them, compound 33 had better inhibitory activity on Src kinase and iNOS, and also significantly inhibited the proliferation of HepG2 and HT-29 cells.