title: 2-Phenylbenzofuran derivatives as butyrylcholinesterase inhibitors: Synthesis, biological activity and molecular modeling.
abstract: A series of 2-phenylbenzofurans compounds was designed, synthesized and evaluated as cholinesterase inhibitors. The biological assay experiments showed that most of the compounds displayed a clearly selective inhibition for butyrylcholinesterase (BChE), while a weak or no effect towards acetylcholinesterase (AChE) was detected. Among these benzofuran derivatives, compound 16 exhibited the highest BChE inhibition with an IC50 value of 30.3 μM. This compound was found to be a mixed-type inhibitor as determined by kinetic analysis. Moreover, molecular dynamics simulations revealed that compound 16 binds to both the catalytic anionic site (CAS) and peripheral anionic site (PAS) of BChE and it displayed the best interaction energy value, in agreement with our experimental data.
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Giovanna L
authors.initials: GL
authors.lastname: Delogu
authors.affiliation: Department of Organic Chemistry, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Matos
authors.affiliation: Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Maura
authors.initials: M
authors.lastname: Fanti
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Era
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Medda
authors.affiliation: Biomedicine Department, Center for Advanced Studies, Research and Development in Sardinia (CRS4), Pula, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Pieroni
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy. Electronic address: fais@unica.it.
authors.forename: Antonella
authors.initials: A
authors.lastname: Fais
authors.affiliation: Biomedicine Department, Center for Advanced Studies, Research and Development in Sardinia (CRS4), Pula, Italy; Department of Mechanical, Chemical and Materials Engineering, University of Cagliari, Cagliari, Italy. Electronic address: amit369@gmail.com.
authors.forename: Amit
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Pintus
mesh_terms: D001572:Benzofurans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002091:Butyrylcholinesterase / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular
chemical_list: D001572:Benzofurans; D002800:Cholinesterase Inhibitors; D002091:Butyrylcholinesterase; C105430:benzofuran
keywords: Acetylcholinesterase; Alzheimer’s disease; Benzofurans; Butyrylcholinesterase; Cholinesterase inhibitors; Docking; Molecular dynamics