Some fused heterocyclic compounds as eukaryotic topoisomerase II inhibitors.
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.
Pinar
Asli
A
Department of Biochemistry, Faculty of Medicine, Hacettepe University, 06100 Ankara, Turkey.
Yurdakul
Pinar
P
Yildiz
Ilkay
I
Temiz-Arpaci
Ozlem
O
Acan
N Leyla
NL
Aki-Sener
Esin
E
Yalcin
Ismail
I
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
D004791:Enzyme Inhibitors; D006571:Heterocyclic Compounds; D059005:Topoisomerase II Inhibitors; D004250:DNA Topoisomerases, Type II