Design, synthesis, <i>in silico</i>, anticancer evaluations of <i>N</i>-acylhydrazone derivatives as STAT3 inhibitors

<i>N</i>-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 <i>N</i>-acylhydrazones (<b>5a-5l</b>) 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 <b>5l</b>. 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 <b>5l</b> and <b>5h</b>. Further, <b>5l</b> 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.