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Published on: February 1, 2011
Exploring the Biological Activity of a Library of 1,2,5-Oxadiazole Derivatives Endowed With Antiproliferative
Arianna Gelain1, Matteo Mori1, Fiorella Meneghetti1
1Department of Pharmaceutical Sciences, University of Milan, Milan, Italy.
Background/Aim:
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 anti-topoisomerase agents.
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