title: Some fused heterocyclic compounds as eukaryotic topoisomerase II inhibitors.
abstract: Our previously synthesized 37 compounds, which are 2,5,6-substituted benzoxazole, benzimidazole, benzothiazole, and oxazolo(4,5-b)pyridine derivatives, were tested for their eukaryotic DNA topoisomerase II inhibitory activity in cell free system and 28 were found to inhibit the topoisomerase II at an initial concentration of 100 microg/ml. After further testing at a lower range of concentrations, 12 derivatives, which were considered as positive topoisomerase inhibitors, exhibited IC50 values between 11.4 and 46.8 microM. Etoposide was used as the standard reference drug to compare the inhibitor activity. Among these compounds, 2-phenoxymethylbenzothiazole (3f), 6-nitro-2-(2-methoxyphenyl)benzoxazole (1a), 5-methylcarboxylate-2-phenylthiomethylbenzimidazole (3c), and 6-methyl-2-(2-nitrophenyl)benzoxazole (1c) were found to be more active than the reference drug etoposide. Present results point out that, besides the very well-known bi- and ter-benzimidazoles, compounds with single bicycle fused ring systems in their structure such as benzimidazole, benzoxazole, benzothiazole, and/or oxazolopyridine derivatives also exhibit significant topoisomerase II inhibitory activity.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Hacettepe University, 06100 Ankara, Turkey.
authors.forename: Asli
authors.initials: A
authors.lastname: Pinar
authors.forename: Pinar
authors.initials: P
authors.lastname: Yurdakul
authors.forename: Ilkay
authors.initials: I
authors.lastname: Yildiz
authors.forename: Ozlem
authors.initials: O
authors.lastname: Temiz-Arpaci
authors.forename: N Leyla
authors.initials: NL
authors.lastname: Acan
authors.forename: Esin
authors.initials: E
authors.lastname: Aki-Sener
authors.forename: Ismail
authors.initials: I
authors.lastname: Yalcin
mesh_terms: D000818:Animals; D004250:DNA Topoisomerases, Type II / Q000737:chemistry; D004331:Drosophila melanogaster / Q000737:chemistry / Q000235:genetics; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000737:chemistry; D005057:Eukaryotic Cells / Q000737:chemistry; D006571:Heterocyclic Compounds / Q000737:chemistry*; D010957:Plasmids / Q000737:chemistry*; D059005:Topoisomerase II Inhibitors
chemical_list: D004791:Enzyme Inhibitors; D006571:Heterocyclic Compounds; D059005:Topoisomerase II Inhibitors; D004250:DNA Topoisomerases, Type II