Novel amphiphilic pyridinium ionic liquids-supported Schiff bases: Ultrasound assisted synthesis, molecular docking and anticancer evaluation

Abstract

Background: Pyridinium Schiff bases and ionic liquids have attracted increasing interest in medicinal chemistry. Results: A library of 32 cationic fluorinated pyridinium hydrazone-based amphiphiles tethering fluorinated counteranions was synthesized by alkylation of 4-fluoropyridine hydrazone with various long alkyl iodide exploiting lead quaternization and metathesis strategies. All compounds were assessed for their anticancer inhibition activity towards different cancer cell lines and the results revealed that increasing the length of the hydrophobic chain of the synthesized analogues appears to significantly enhance their anticancer activities. Substantial increase in caspase-3 activity was demonstrated upon treatment with the most potent compounds, namely 8, 28, 29 and 32 suggesting an apoptotic cellular death pathway. Conclusions: Quantum-polarized ligand docking studies against phosphoinositide 3-kinase α displayed that compounds 2-6 bind to the kinase site and form H-bond with S774, K802, H917 and D933.