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

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

  • Bioorg Med Chem. 2016 Oct 1;24(19):4731-4740. doi: 10.1016/j.bmc.2016.08.016.
Hui Li 1,  Yan Hu 2,  Xueyan Wang 1,  Guangwei He 3,  Yungen Xu 4,  Qihua Zhu 4
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, China.
  • 2 Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 21009, China.
  • 3 Hefei YiGong Pharmaceutical Co. Ltd, Hefei 230088, China.
  • 4 Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, China; Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 21009, China.
PMID: 27561983 DOI: 10.1016/j.bmc.2016.08.016
Abstract

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 28nM in the PARP-1 and 7.7nM 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.

Keywords

Anticancer; Inhibitors; PARP-1/2; Tricyclic.

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