The therapeutic strategy of poly (ADP-ribose) polymerase (PARP) inhibition of BRCA1/2 mutant cancers has been overwhelmingly successful, however, the highly aggressive triple negative breast cancers (TNBC) that receptor protein tyrosine kinase (RTKs) is known to be overexpressed are not sensitive to PARP inhibitors. Our research focused on exploring PARP inhibitors incorporating a bicyclic tetrahydropyridine pyrimidine. All synthesized compounds were more potent than Olaparib (ola) in killing tumor cells, especially in TNBC. Furthermore, compound 7 exhibited strong inhibitory effects on PARP enzymatic activity, moreover, the expression of EGFR and phosphorylated EGFR was inhibited by compound 7. Therefore, compound 7 can effectively inhibit TNBC cells with high expression of EGFR. In addition, significant synergistic effect of anti-tumor effect of new PARP inhibitors and adriamycin was also observed.

聚 (ADP-核糖) 聚合酶 (PARP) 抑制 BRCA1/2 突变癌症的治疗策略取得了压倒性的成功，然而，受体蛋白酪氨酸激酶 (RTK) 已知是高度侵袭性的三阴性乳腺癌 (TNBC)过表达对 PARP 抑制剂不敏感。我们的研究重点是探索含有双环四氢吡啶嘧啶的 PARP 抑制剂。所有合成的化合物在杀死肿瘤细胞方面都比奥拉帕尼 (ola) 更有效，尤其是在 TNBC 中。此外，化合物7对PARP酶活性有很强的抑制作用，而且化合物7抑制EGFR和磷酸化EGFR的表达。因此，化合物7可以有效抑制EGFR高表达的TNBC细胞。此外，