title: Some benzoxazoles and benzimidazoles as DNA topoisomerase I and II inhibitors.
abstract: Some novel fused heterocyclic compounds of 2, 5-disubstituted-benzoxazole and benzimidazole derivatives, which were previously synthesized by our group, were investigated for their inhibitory activity on both eukaryotic DNA topoisomerase I and II in a cell free system. 2-Phenoxymethylbenzimidazole (17), 5-amino-2-(p-fluorophenyl)benzoxazole (3), 5-amino-2-(p-bromophenyl)benzoxazole (5), 5-nitro-2-phenoxymethyl-benzimidazole (18), 2-(p-chlorobenzyl)benzoxazole (10) and 5-amino-2-phenylbenzoxazole (2) were found to be more potent as eukaryotic DNA topoisomerase I poisons than the reference drug camptothecin having IC(50) values of 14.1, 132.3, 134.1, 248, 443.5, and 495 microM, respectively. 5-Chloro-2-(p-methylphenyl)benzoxazole (4), 2-(p-nitrobenzyl)benzoxazole (6) and 5-nitro-2-(p-nitrobenzyl)benzoxazole (8) exhibited significant activity as eukaryotic DNA topoisomerase II inhibitors, having IC(50) values of 22.3, 17.4, 91.41 microM, respectively, showing higher potency than the reference drug etoposide.
authors.affiliation: Molecular Biology Department, Hacettepe University, Ankara, Beytepe, Turkey.
authors.forename: Emine
authors.initials: E
authors.lastname: Oksuzoglu
authors.forename: Betul
authors.initials: B
authors.lastname: Tekiner-Gulbas
authors.forename: Sabiha
authors.initials: S
authors.lastname: Alper
authors.forename: Ozlem
authors.initials: O
authors.lastname: Temiz-Arpaci
authors.forename: Tugba
authors.initials: T
authors.lastname: Ertan
authors.forename: Ilkay
authors.initials: I
authors.lastname: Yildiz
authors.forename: Nuran
authors.initials: N
authors.lastname: Diril
authors.forename: Esin
authors.initials: E
authors.lastname: Sener-Aki
authors.forename: Ismail
authors.initials: I
authors.lastname: Yalcin
mesh_terms: D001562:Benzimidazoles / Q000494:pharmacology*; D001583:Benzoxazoles / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors
chemical_list: D001562:Benzimidazoles; D001583:Benzoxazoles; D004791:Enzyme Inhibitors; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D005047:Etoposide