title: Tricyclic benzimidazoles as potent poly(ADP-ribose) polymerase-1 inhibitors.
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.
authors.affiliation: Pfizer Global R&D, La Jolla/Agouron Pharmaceuticals, Inc., San Diego, California 92121, USA.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Skalitzky
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Marakovits
authors.forename: Karen A
authors.initials: KA
authors.lastname: Maegley
authors.forename: Anne
authors.initials: A
authors.lastname: Ekker
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Yu
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Hostomsky
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Webber
authors.forename: Brian W
authors.initials: BW
authors.lastname: Eastman
authors.forename: Robert
authors.initials: R
authors.lastname: Almassy
authors.forename: Jianke
authors.initials: J
authors.lastname: Li
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Curtin
authors.forename: David R
authors.initials: DR
authors.lastname: Newell
authors.forename: A Hilary
authors.initials: AH
authors.lastname: Calvert
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Griffin
authors.forename: Bernard T
authors.initials: BT
authors.lastname: Golding
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D002460:Cell Line; D018360:Crystallography, X-Ray; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D000077204:Temozolomide; D019772:Topotecan / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D006575:Heterocyclic Compounds, 3-Ring; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011355:Prodrugs; D003606:Dacarbazine; D019772:Topotecan; D000077204:Temozolomide