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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1240-1253
Number of pages14
JournalChemistry and Biodiversity
Volume9
Issue number7
DOIs
Publication statusPublished - Jul 2012

Keywords

  • 1,2,5-Oxadiazoles, ureido-
  • Inhibitors
  • Signal transducer and activator of transcription 3 (STAT3)
  • Structure-activity relationship (SAR)
  • X-Ray crystallography

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)
  • Bioengineering
  • Molecular Biology
  • Molecular Medicine

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