Key points are not available for this paper at this time.
This study focuses on the development of novel sulphonyl chalcone-based Pyrimidinone derivatives as potential anticholinesterase agents for the treatment of Alzheimer’s Disease. A series of sulphonyl pyrimidinone derivatives were synthesized, affording yields in the range from 60-75%, thoroughly characterized by using different physicochemical and spectral techniques, and evaluated for in-vitro acetylcholinesterase (AChE) inhibitory activity, antioxidant activity, and cognitive enhancing effect using a scopolamine-induced mouse model. Among the synthesized compounds 4e, and 4f demonstrated strong AChE inhibition with IC50 Values of 74.00±2.08 μM and 70.66±1.45 μM respectively, outperforming the standard drug Donepezil (IC50 = 89.00 ± 2.00 μM). Furthermore, compound 4f also demonstrated superior antioxidant activity with an IC50 value of 21.403 ± 0.596 μM, surpassing that of the standard ascorbic acid (IC50 value of 23.807±0.421 μM), suggesting its dual neuroprotective potential. The enhanced AChE inhibition and antioxidant potential of these compounds can be attributed to the presence of an electrondonating group i.e. alkyl moiety. In addition, cognitive-enhancing effects observed in the in-vivo scopolamine-induced mouse model were consistent with the in-vitro results, supporting the potential of compounds 4e and 4f. Molecular docking simulations further confirmed the strong binding interactions of these compounds with AChE (PDB:4ey7), supporting their mechanism of action. Collectively, these findings present sulphonyl chalcone-based pyrimidine hybrids as promising therapeutic leads for the development of multi-functional agents for Alzheimer’s disease treatment.
Dewangan et al. (Fri,) studied this question.