2. Academic Validation
  3. Design, synthesis and biological evaluation of novel 5-fluoro-1H-benzimidazole-4-carboxamide derivatives as potent PARP-1 inhibitors

Design, synthesis and biological evaluation of novel 5-fluoro-1H-benzimidazole-4-carboxamide derivatives as potent PARP-1 inhibitors

  • Bioorg Med Chem Lett. 2016 Aug 15;26(16):4127-32. doi: 10.1016/j.bmcl.2016.06.045.
Junwei Wang 1,  Xuyan Wang 2,  Hui Li 3,  Dezhong Ji 3,  Yuyan Li 2,  Yungen Xu 1,  Qihua Zhu 1
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
  • 2 Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
  • 3 Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.
PMID: 27353531 DOI: 10.1016/j.bmcl.2016.06.045
Abstract

A series of novel 5-fluorine-benzimidazole-4-carboxamide analogs were designed and synthesized. All target compounds were evaluated for their PARP-1 inhibitory activity. Compounds possessed high intrinsic PARP-1 inhibitory potency have been evaluated in vitro cellular assays to measure the potentiation effect of cytotoxic agents against Cancer cell line. These efforts led to the identification of compound 10f, which displayed strong inhibition against the PARP-1 Enzyme with an IC50 of 43.7nM, excellent cell inhibitory activity in HCT116 cells (IC50=7.4μM) and potentiation of temozolomide cytotoxicity in Cancer cell line A549 (PF50=1.6).

Keywords

Antitumor; Benzimidazole; Fluorine atom; Inhibitors; PARP-1.

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