Synthesis of 1,2,4-triazole and 1,3,4-oxadiazole derivatives as inhibitors for STAT3 enzymes of breast cancer

Arch Pharm (Weinheim). 2023 Nov;356(11):e2300345. doi: 10.1002/ardp.202300345. Epub 2023 Sep 3.

Abstract

Disubstituted five-membered heterocycles (1,2,4-triazole and 1,3,4 oxadiazole) were synthesized and investigated as inhibitors for signal transducer and activator of transcription 3 (STAT3) enzyme of breast cancer. 3-(Benzylthio)-5-(4-chlorobenzyl)-4H-1,2,4-triazol-4-amine (12d) was found to be the most active among the synthesized compounds with a half-maximal inhibitory concentration (IC50 ) value of 1.5 µM on MCF7 cells and was found to show a great inhibitory effect on the STAT3 enzyme. Compounds 9a,b,d,e,f, 11, and 12a,b,f,e show IC50 values in the range of 3-12 µM for the MCF7 cell line. Molecular modeling was used to investigate the biological results of the synthesized compounds.

Keywords: STAT3; breast cancer; docking; oxadiazoles; triazoles.

MeSH terms

  • Breast Neoplasms* / drug therapy
  • Female
  • Humans
  • Molecular Docking Simulation
  • Molecular Structure
  • Oxadiazoles / pharmacology
  • STAT3 Transcription Factor
  • Structure-Activity Relationship

Substances

  • 1,3,4-oxadiazole
  • 1,2,4-triazole
  • STAT3 Transcription Factor
  • Oxadiazoles
  • STAT3 protein, human