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.

Exploring the biological activity of a library of 1,2,5-oxadiazole derivatives endowed with antiproliferative activity / A. Gelain, M. Mori, F. Meneghetti, F. Porta, L. Basile, G. Marverti, A. Asai, M. Hyeraci, A.N. García-Argáez, L.D. Via, S. Guccione, S. Villa. - In: ANTICANCER RESEARCH. - ISSN 0250-7005. - 39:1(2019 Jan), pp. 135-144. [10.21873/anticanres.13089]

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

A. Gelain
Primo
;
M. Mori;F. Meneghetti;F. Porta;S. Villa
Ultimo
2019-01

Abstract

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.
Cytotoxicity; Docking studies; HCT-116; HeLa; Oxadiazoles; Topoisomerase I; Oncology; Cancer Research
Settore CHIM/08 - Chimica Farmaceutica
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/632615
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