Background: A series of 2-substituted benzoxazoles and their possible metabolites,
N-(2-hydroxy-4(or 5)-nitrophenyl)benzamides and phenylacetamides, which were previously
synthesized by our group, were investigated for their inhibitory activities on both eukaryotic DNA
topoisomerase I (Topo I) and II (Topo II).
Methods: DNA topoisomerase I and II inhibitory activity of compounds were determined by relaxation
assay which could measure the conversion of supercoiled pBR322 plasmid DNA to its
Results: According to DNA topoisomerase relaxation assay results, four derivatives (1c, 1f, 2b, 2e)
among tested 21 compounds inhibited human Topo I, whereas three compounds (1c, 1e, 1f) inhibited
human Topo IIα. 2-(4’-bromophenyl)-6-nitrobenzoxazole (1f) was observed to be the most
effective Topo II inhibitor with the lowest IC50 value of 71 µM and 2-(4’-tert-butyl-phenyl)-6-
nitrobenzoxazole (1c) with the IC50 value of 104 µM was considered the most effective Topo I inhibitor.
However, it is noteworthy that these two compounds affected both Topo I and II enzymes.
When the relationship between chemical structures and biological activities of the compounds were
examined, the following two results were obtained: (i) CH2 bridge seems to decrease the Topo I and
II inhibitions and (ii) bulky groups at R1 position increased both Topo I and II inhibitions for benzoxazole
derivatives while small groups at R1 position increased the Topo I inhibition for benzamide
Conclusion: Biological activity and SAR results of tested derivatives may provide some predictions
in order to design novel topoisomerase inhibitors.