Design, synthesis and biological evaluation of novel 3-(2-oxo-2-substituted acetamido)benzamides as PARP-1 inhibitors.
- Author:
Yu-wen YIN
;
Ming JI
;
Ran CAO
;
Xiao-guang CHEN
;
Bai-ling XU
- Publication Type:Journal Article
- MeSH:
Antineoplastic Agents;
Benzamides;
chemistry;
DNA Repair;
Drug Design;
Humans;
Molecular Docking Simulation;
Poly(ADP-ribose) Polymerase Inhibitors;
chemical synthesis;
chemistry;
Poly(ADP-ribose) Polymerases
- From:
Acta Pharmaceutica Sinica
2015;50(6):738-745
- CountryChina
- Language:Chinese
-
Abstract:
Poly(ADP-ribose)polymerase-1 (PARP-1) plays a significant role in the DNA repair process by catalyzing the transfer of ADP-ribose from NAD+ to its receptors. It is a promising anticancer drug target and many PARP-1 inhibitors have been developed and used in the clinical trial. In this work, a series of 3-(2-oxo-2-substituted acetamido)benzamides have been synthesized and their inhibitory activities against PARP-1 were evaluated. Of all the tested compounds, six compounds displayed inhibitory activities with IC50 values ranging from 0.23 to 5.78 µmol.L-1 . The binding pose of compound 5a was predicted using molecular docking to facilitate further structural modification.
