Arylhydrazineylidene linked dimedone and acetylacetone analogs as multitarget inhibitors of α -glucosidase, α -amylase, acetylcholinesterase, butyrylcholinesterase and potential antioxidants: an integrated study based on synthesis, in vitro study, molecular docking, and ADME analysis

BACKGROUND: Diabetes and Alzheimer diseases have the shared pathological mechanisms, thus making multitarget-directed inhibitors as a promising therapeutic approach. METHODS: In the present study, a varyingly substituted arylhydrazineylidene linked dimedone and acetylacetone analogs 1-32 were synthesized, characterized, and first time evaluated against α-amylase, α-glucosidase, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) enzymes. RESULTS: values of 1.59, 1.90, 1.94, and 2.14 µM against α-amylase, α-glucosidase, AChE, and BChE, respectively. Compounds were also evaluated for antioxidant potential and luckily compound 13 was found to possess strong antioxidant potential. Other compounds also demonstrated notable activity, whereas a few were found inactive. Furthermore, the compounds were subjected to molecular docking studies to reveal their binding interactions with the target enzymes and to rationalize their observed inhibitory activities. Moreover, a comprehensive pharmacokinetics, drug-likeness, and ADME analysis was also predicted. The synthesized compounds have optimal oral absorption and bioavailability. CONCLUSION: This study has identified promising multitarget inhibitors that could be potential therapeutics for the treatment of diabetes and Alzheimer disease.