Novel Benzamide Derivatives: Synthesis and Bioactivity as Potent PARP‐1 Inhibitors

Citations Over Time

Abstract

The poly( ADP ‐ribose) polymerases ( PARPs ) are located in the nuclei of cells and involved in DNA damage repair. PARP inhibitors have been used to target BRCA1 /2‐defective cells that experience increases in DNA single‐strand breaks ( SSBs ). In the presence of PAPR inhibitors, these SSBs are converted into irreparable and toxic double‐strand breaks ( DSBs ) during replication, eventually leading to cell death due to genome instability caused by the impaired homologous‐mediated repair system. We designed and synthesized several novel benzamide derivatives based on the previously reported PARP ‐1‐inhibitory activities of benzoxazole and benzamide moieties. Next, we used an in vitro assay to quantify their PARP ‐1 inhibitory activity and evaluate their potential as possible anti‐cancer therapeutics. Compound 28d contains a hydroxamate group and showed a significant inhibitory capacity ( IC 50 value of 3.2 μM ; 2.8‐ and 4.2‐fold decrease in SNU ‐251 and MDA‐MB ‐231 cells, respectively, compared with the DMSO ‐treated controls). Based on these results, we suggest that we have identified a novel hydroxybenzamide derivative of a benzamide moiety which is known as a key pharmacophore in existing PARP inhibitors.

Related Papers

• → NADH can enter into astrocytes and block poly(ADP-ribose) polymerase-1-mediated astrocyte death(2005)39 cited
• → Novel Benzamide Derivatives: Synthesis and Bioactivity as Potent PARP‐1 Inhibitors(2017)7 cited
• → Complete inhibition of poly(ADP-ribose) polymerase activity prevents the recovery of C3H1OT1/2 cells from oxidative stress(1996)32 cited
• Protective effect of poly(ADP-ribose) polymerase inhibitor benzamide aganist neuronal damage induced by 3-nitropropionic acid in rat striatum 랫트 선조체에서 3-Nitropropionic acid에 의한 신경손상에 대한 ADP-ribose 중합효소 억제제인 benzamide의 보호 효과(2000)
• Benzamide prevents glioma cell line from apoptosis induced by MNNG(2000)