Inhibitors of poly (ADP-ribose) polymerase-1 (PARP-1) have shown to be promising in clinical trials against cancer, and many researchers are interested in the development of new PARP-1 inhibitors. Herein, we designed and synthesized 44 novel erythrina derivatives bearing a 1,2,3-triazole moiety as PARP-1 inhibitors. MTT assay results indicated that compound 10b had the most potent anti-proliferative activity against A549 cells among five cancer cells. The enzyme inhibitory activity in vitro of compound 10b was also significantly better than rucaparib. Furthermore, the selectivity index of compound 10b was higher than rucaparib for lung cancer cells. Flow cytometry analysis showed that compound 10b induced apoptosis of A549 cells by the mitochondrial pathway. Western blot analysis indicated that compound 10b was able to inhibit the biosynthesis of PAR effectively, and it was more potent than rucaparib. Also, compound 10b was able to up-regulate the ratio of bax/bcl-2, activate caspase-3, and ultimately induced apoptosis of A549 cells. The combined results revealed that the discovery of novel non-amide based PARP-1 inhibitors have great research significance and provide a better choice for the future development of drugs.

中文翻译：

---

设计，合成和生物学评估作为PARP-1抑制剂的带有1,2,3-三唑部分的赤藓衍生物。

聚（ADP-核糖）聚合酶-1（PARP-1）的抑制剂在抗癌的临床试验中已显示出前景广阔，许多研究人员对新型PARP-1抑制剂的开发感兴趣。在这里，我们设计和合成了44个带有1,2,3-三唑部分的新型赤藓类衍生物作为PARP-1抑制剂。MTT测定结果表明，化合物5b在五个癌细胞中对A549细胞具有最有效的抗增殖活性。化合物10b的体外酶抑制活性也明显优于rucaparib。此外，化合物10b对肺癌细胞的选择性指数高于rucaparib。流式细胞仪分析表明，化合物10b通过线粒体途径诱导A549细胞凋亡。Western印迹分析表明，化合物10b能够有效抑制PAR的生物合成，并且比rucaparib更有效。同样，化合物10b能够上调bax / bcl-2的比例，激活caspase-3，并最终诱导A549细胞凋亡。综合结果表明，新型基于非酰胺的PARP-1抑制剂的发现具有重要的研究意义，并为药物的未来发展提供了更好的选择。