A New Class of Benzo[<em>b</em>]thiophene-chalcones as Cholinesterase Inhibitors: Synthesis, Biological Evaluation, Molecular Docking and ADME Studies
Giovanna Lucia Delogu,
Michela Begala,
Maria João Matos,
Davide Crucitti,
Valeria Sogos,
Benedetta Era,
Antonella Fais
Affiliations
Giovanna Lucia Delogu
Department of Live and Environmental Sciences, University of Cagliari, Cittadella Universitaria, SS 554, Km 4.5, 09042 Monserrato, Italy
Michela Begala
Department of Live and Environmental Sciences, University of Cagliari, Cittadella Universitaria, SS 554, Km 4.5, 09042 Monserrato, Italy
Maria João Matos
Departamento de Química Orgánica, Facultad de Farmacia, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain
Davide Crucitti
Group of Computational Genomics and Hematology (GreCoXen), Health Research Institute of Santiago de Compostela (IDIS), 15782 Santiago de Compostela, Spain
Valeria Sogos
Department of Biomediacal Science, University of Cagliari, Cittadella Universitaria, SS 554, Km 4.5, 09042 Monserrato, Italy
Benedetta Era
Department of Live and Environmental Sciences, University of Cagliari, Cittadella Universitaria, SS 554, Km 4.5, 09042 Monserrato, Italy
Antonella Fais
Department of Live and Environmental Sciences, University of Cagliari, Cittadella Universitaria, SS 554, Km 4.5, 09042 Monserrato, Italy
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 (IC50 = 62.10 μM) and compound 5h being the best BChE inhibitor (IC50 = 24.35 μM), the last one having an IC50 similar to that of galantamine (IC50 = 28.08 μM), 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.
