Novel tricyclic poly (ADP-ribose) polymerase-1/2 inhibitors with potent anticancer chemopotentiating activity: Design, synthesis and biological evaluation

作者：Li, Hui; Hu, Yan; Wang, Xueyan; He, Guangwei; Xu, Yungen^*; Zhu, Qihua^*

来源：Bioorganic & Medicinal Chemistry, 2016, 24(19): 4731-4740.

DOI：10.1016/j.bmc.2016.08.016

• PARP-1/2
• Inhibitors
• Tricyclic
• Anticancer

8,9-Dihydro-2,4,7,9a-tetraazabenzo[cd]azulen-6(7H)-ones were designed and synthesized as a new class of PARP-1/2 inhibitors. The compounds displayed a variable pattern of PARP-1/2 enzymes inhibition profile that, in part, paralleled the antiproliferative activity in cell lines. Among them, compound 9e exhibited not only the significant IC50 value of 28 nM in the PARP-1 and 7.7 nM in PARP-2 enzyme assay, but also a profound synergic efficacy combined with temozolomide with PF50 values of 2.6, 2.5, and 6.5 against MDA-MB-468, SW-620 and A549 and cell line, respectively.

• 出版日期2016-10-1
• 单位中国药科大学