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

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.