Design, synthesis, in silico, anticancer evaluations of N-acylhydrazone derivatives as STAT3 inhibitors

N-acylhydrazone derivatives were synthesized, evaluated in-vitro and further subjected to cell cycle analysis, cell apoptosis, western bloting, and in-silico analysis targeting STAT3.

A series of N-acylhydrazones (5a-5l) were synthesized and evaluated against MIA PaCa-2 cancer cells. 5 h and 5 l were further evaluated against PANC-1, MCF-7 and hTERT-HPNE cells. Additionally, cell cycle analysis, apoptosis, western blotting, docking, in-silico ADMET, molecular dynamics and MM-GBSA were done on 5l.

5 l and 5 h suppressed the growth of MIA PaCa-2 cancer cells and were very less cytotoxic to hTERT-HPNE cells. Additionally, the anticancer efficacy was confirmed against PANC-1 and MCF-7 for 5l and 5h. Further, 5l treatment induced G1/S arrest marked decrease in G2/M and displayed a significant increase in the apoptosis of MIA PaCa-2 cells. 5 l treatment significantly inhibited the phosphorylated level STAT3 and JAK1. In-silico studies confirm the binding affinity and stability and further synthetic modifications and biological investigations can be done to explore the medicinal potential of the derivatives in future.