Delogu_2024_Molecules_29_

In this study, heterocyclic compounds containing a benzothiophene scaffold were designed and synthetized, and their inhibitory activity against cholinesterases (ChE) and the viability of SH-SY5Y cells have been evaluated. Benzothiophenes 4a-4i and benzothiophene-chalcone hybrids 5a-5i were tested against both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), revealing interesting structure-activity relationships. In general, benzothiophene-chalcone hybrids from series 5 proved to be better inhibitors of both enzymes, with compound 5f being the best AChE inhibitor (IC(50) = 62.10 microM) and compound 5h being the best BChE inhibitor (IC(50) = 24.35 microM), the last one having an IC(50) similar to that of galantamine (IC(50) = 28.08 microM), the reference compound. The in silico ADME profile of the compounds was also studied. Molecular docking calculations were carried out to analyze the best binding scores and to elucidate enzyme-inhibitors' interactions.