The influence of the substitution pattern on the molecular conformation of ureido-1,2,5-oxadiazoles, related to STAT3 inhibitors: chemical behavior and structural investigation.

Stefania Villa, Daniela Masciocchi, Arianna Gelain, Fiorella Meneghetti

Department of Pharmaceutical Sciences Pietro Pratesi, University of Milan, Milano, Italy.

Chemistry & biodiversity 2012 Jul

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Signal transducer and activator of transcription 3 (STAT3) is a protein constitutively activated by aberrant upstream tyrosine kinase activities in a broad spectrum of human solid and blood tumors. Therefore, the availability of drugs affecting STAT3 may have important therapeutic potential for the treatment of cancer. Pursuing our efforts in exploring the influence of the substitution pattern of the ureido 1,2,5-oxadiazole moiety on the molecular conformation, new compounds substituted at positions 3 and 4 on the furazane ring were synthesized. The inhibition properties vs. STAT3 of the novel compounds were evaluated in a dual-luciferase assay, using HCT-116 cells, and the results evidenced a moderate activity only for the compounds endowed with a planar arrangement. Crystallographic studies of the new derivatives were performed in order to evidence the peculiar chemical behavior and to evaluate how structural modulations affected the biological properties. Copyright © 2012 Verlag Helvetica Chimica Acta AG, Zürich.

Citation

Stefania Villa, Daniela Masciocchi, Arianna Gelain, Fiorella Meneghetti. The influence of the substitution pattern on the molecular conformation of ureido-1,2,5-oxadiazoles, related to STAT3 inhibitors: chemical behavior and structural investigation. Chemistry & biodiversity. 2012 Jul;9(7):1240-53