Design, synthesis and biological evaluation of novel para-substituted 1-benzyl-quinazoline-2, 4 (1H, 3H)-diones as human PARP-1 inhibitors / 药学学报
Acta Pharmaceutica Sinica
; (12): 497-503, 2014.
Article
in Zh
| WPRIM
| ID: wpr-245056
Responsible library:
WPRO
ABSTRACT
Poly(ADP-ribose) polymerase-1 (PARP-1) has emerged as a promising anticancer drug target due to its key role in the DNA repair process. It can polymerize ADP-ribose units on its substrate proteins which are involved in the regulation of DNA repair. In this work, a novel series of para-substituted 1-benzyl-quinazoline-2, 4 (1H, 3H)-diones was designed and synthesized, and the inhibitory activities against PARP-1 of compounds 7a-7e, 8a-8f, 9a-9c and 10a-10c were evaluated. Of all the tested compounds, nine compounds displayed inhibitory activities with IC50 values ranging from 4.6 to 39.2 micromol x L(-1). In order to predict the binding modes of the potent molecules, molecular docking was performed using CDOCKER algorithm, and that will facilitate to further develop more potent PARP-1 inhibitors with a quinazolinedione scaffold.
Full text:
1
Index:
WPRIM
Main subject:
Pharmacology
/
Structure-Activity Relationship
/
Drug Design
/
Molecular Structure
/
Chemistry
/
Poly(ADP-ribose) Polymerases
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Enzyme Inhibitors
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Quinazolinones
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Molecular Docking Simulation
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Poly (ADP-Ribose) Polymerase-1
Type of study:
Prognostic_studies
Language:
Zh
Journal:
Acta Pharmaceutica Sinica
Year:
2014
Type:
Article