Abstract
A series of benzimidazole carboxamide derivatives have been synthesized and characterized by 1H-NMR, 13C-NMR and HRMS. PARP inhibition assays and cellular proliferation assays have also been carried out. Compounds 5cj and 5cp exhibited potential anticancer activities with IC50 values of about 4 nM against both PARP-1 and PARP-2, similar to the reference drug veliparib. The two compounds also displayed slightly better in vitro cytotoxicities against MDA-MB-436 and CAPAN-1 cell lines than veliparib and olaparib, with values of 17.4 µM and 11.4 µM, 19.8 µM and 15.5 µM, respectively. The structure-activity relationship based on molecular docking was discussed as well.
Keywords:
PARP enzyme inhibition; benzimidazole carboxamide; poly(ADP-ribose) polymerase.
MeSH terms
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Cell Survival / drug effects
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Drug Discovery
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Drug Screening Assays, Antitumor
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Humans
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Imidazoles / chemical synthesis*
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Imidazoles / chemistry
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Imidazoles / pharmacology*
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Models, Molecular
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Molecular Docking Simulation
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Neoplasms / drug therapy
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Neoplasms / metabolism*
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Poly (ADP-Ribose) Polymerase-1 / antagonists & inhibitors
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Poly (ADP-Ribose) Polymerase-1 / chemistry
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Poly(ADP-ribose) Polymerase Inhibitors / chemical synthesis*
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Poly(ADP-ribose) Polymerase Inhibitors / chemistry
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Poly(ADP-ribose) Polymerase Inhibitors / pharmacology*
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Poly(ADP-ribose) Polymerases / chemistry
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Poly(ADP-ribose) Polymerases / metabolism
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Structure-Activity Relationship
Substances
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Imidazoles
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Poly(ADP-ribose) Polymerase Inhibitors
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PARP1 protein, human
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PARP2 protein, human
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Poly (ADP-Ribose) Polymerase-1
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Poly(ADP-ribose) Polymerases