Portal de Periódicos da CAPES

Some fused heterocyclic compounds as eukaryotic topoisomerase II inhibitors

2004; Elsevier BV; Volume: 317; Issue: 2 Linguagem: Inglês

10.1016/j.bbrc.2004.03.093

1090-2104

Aslı Pınar, Pınar Yurdakul, İlkay Yıldız, Özlem Temiz‐Arpacı, N. Leyla Açan, Esin Aki, İsmail Yalçın,

Synthesis and bioactivity of alkaloids

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 μg/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 μM. 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.