Abstract
Novel tricyclic benzimidazole carboxamide poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors have been synthesized. Several compounds were found to be powerful chemopotentiators of temozolomide and topotecan in both A549 and LoVo cell lines. In vitro inhibition of PARP-1 was confirmed by direct measurement of NAD+ depletion and ADP-ribose polymer formation caused by chemically induced DNA damage.
MeSH terms
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Benzimidazoles / chemical synthesis*
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Benzimidazoles / chemistry
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Benzimidazoles / pharmacology
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Binding Sites
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Cell Line
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Crystallography, X-Ray
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Dacarbazine / analogs & derivatives*
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Dacarbazine / metabolism
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Dacarbazine / pharmacology
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Drug Resistance, Neoplasm
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology
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Heterocyclic Compounds, 3-Ring / chemical synthesis*
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Heterocyclic Compounds, 3-Ring / chemistry
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Heterocyclic Compounds, 3-Ring / pharmacology
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Humans
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Models, Molecular
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Poly(ADP-ribose) Polymerase Inhibitors*
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Prodrugs / chemical synthesis
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Prodrugs / chemistry
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Prodrugs / pharmacology
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Stereoisomerism
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Structure-Activity Relationship
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Temozolomide
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Topotecan / metabolism
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Topotecan / pharmacology
Substances
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Antineoplastic Agents
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Benzimidazoles
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Enzyme Inhibitors
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Heterocyclic Compounds, 3-Ring
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Poly(ADP-ribose) Polymerase Inhibitors
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Prodrugs
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Dacarbazine
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Topotecan
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Temozolomide