New sulfurated derivatives of cinnamic acids and rosmaricine as inhibitors of STAT3 and NF-κB transcription factors

J Enzyme Inhib Med Chem. 2017 Dec;32(1):1012-1028. doi: 10.1080/14756366.2017.1350658.

Abstract

A set of new sulfurated drug hybrids, mainly derived from caffeic and ferulic acids and rosmaricine, has been synthesized and their ability to inhibit both STAT3 and NF-κB transcription factors have been evaluated. Results showed that most of the new hybrid compounds were able to strongly and selectively bind to STAT3, whereas the parent drugs were devoid of this ability at the tested concentrations. Some of them were also able to inhibit the NF-κB transcriptional activity in HCT-116 cell line and inhibited HCT-116 cell proliferation in vitro with IC50 in micromolar range, thus suggesting a potential anticancer activity. Taken together, our study described the identification of new derivatives with dual STAT3/NF-κB inhibitory activity, which may represent hit compounds for developing multi-target anticancer agents.

Keywords: Anticancer drug; NF-κB inhibitors; STAT3 inhibitors; cytotoxicity; methanethiosulfonate derivatives.

MeSH terms

  • Cell Survival / drug effects
  • Cinnamates / chemical synthesis
  • Cinnamates / chemistry
  • Cinnamates / pharmacology*
  • Diterpenes / chemical synthesis
  • Diterpenes / chemistry
  • Diterpenes / pharmacology*
  • Dose-Response Relationship, Drug
  • HCT116 Cells
  • HeLa Cells
  • Humans
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • STAT3 Transcription Factor / antagonists & inhibitors*
  • STAT3 Transcription Factor / metabolism
  • Structure-Activity Relationship
  • Sulfuric Acids / chemistry
  • Sulfuric Acids / pharmacology*

Substances

  • Cinnamates
  • Diterpenes
  • NF-kappa B
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Sulfuric Acids
  • cinnamic acid
  • rosmaricine

Grants and funding

Italian Ministero dell’Istruzione, dell'Università e della Ricerca (MIUR) [(PRIN 2010-11, code 20105YY2HL)].