Exploring the biological activity of a library of 1,2,5-Oxadiazole derivatives endowed with antiproliferative activity

The identification of a series of
oxadiazole-based compounds, as promising antiproliferative
agents, has been previously reported. The aim of this study
was to explore the SAR of newly-synthesized oxadiazole
derivatives and identify their molecular targets. Materials
and Methods: A small library of 1,2,5-oxadiazole derivatives
was synthetized and their antiproliferative activity was tested
by the MTT assay. Their interaction with topoisomerase I was
evaluated and a molecular docking study was performed.
Results: Several candidates showed cytotoxicity towards two
human tumor cell lines, HCT-116 (colorectal carcinoma) and
HeLa (cervix adenocarcinoma). Some derivatives exhibited
inhibitory effects on the catalytic activity of topoisomerase I
and this effect was supported by docking studies. Conclusion:
The enzyme inhibition results, although not directly related to
cytotoxicity, suggest that a properly modified 1,2,5 oxadiazole
scaffold could be considered for the development of new antitopoisomerase
agents.