New synthetic quinaldine conjugates: Assessment of their anti-cholinesterase, anti-tyrosinase and cytotoxic activities, and molecular docking analysis

Abstract

• Synthesis of new quinoline-succinimide derivatives. • Synthesized derivatives were screened for their anti-tyrosinase and cytotoxic activities. • Compounds 3d , 3e and 3 g showed interesting tyrosinase inhibitory activities. • Compounds 3f , 3 g and 3a displayed the highest activity against HeLa cell lines. • Molecular docking analysis reinforced the experimental results. Despite all the progress made to enrich the existing bank of drugs used to treat and cure Alzheimer and cancer patients, there is still a need to research and develop new bioactive candidates with superior efficacy but minimal side effects. In this context, a new series of anti-butyrylcholinesterase (anti-BChE), anti-tyrosinase and cytotoxic succinimide linked quinaldine conjugates 3a-i was designed and synthesized starting from 8-hydroxyquinaldine. The condensation of quinoleine-hydrazide 2 with electrophilic species such as aromatic and nonaromatic anhydrides provided the new compounds 3a-i . These synthesized heterocycles were characterized by spectroscopic means ( 1 H NMR, 13 C NMR and ESI-HRMS). Their anti-butyrylcholinesterase, anti-tyrosinase and cytotoxic (cervical cancer cell (HeLa) and lung cancer cell (A549)) activities have been evaluated in vitro . Compounds 3e and 3 g were found to be more anti-BChE than Galanthamine. Compounds 3d , 3e and 3 g exerted better anti-tyrosinase activity than kojic acid. Also, 3a , 3f and 3 g showed interesting cytotoxic potential towards HeLa cell lines. These results were supported by the molecular docking analysis (structure–activity relationship (SAR)) to estimate and discuss possible interactions between these derivatives and active sites of proteins butyrylcholinesterase (PDB: 4B0P), tyrosinase (PDB: 2Y9X) and cytotoxic (topoisomerase IIα enzyme (PDB: 5GWK)).