title: Design, synthesis and biological evaluation of novel 6H-benzo[c]chromen-6-one, and 7,8,9,10-tetrahydro-benzo[c]chromen-6-one derivatives as potential cholinesterase inhibitors.
abstract: Hydroxylated 6H-benzo[c]chromen-6-one derivatives (i.e., urolithins) are the main bioavailable metabolites, and biomarkers of ellagitannins present in various nutrition. Although these dietaries, the sources of urolithins, are employed in folk medicine as cognitive enhancer in the treatment of Alzheimer's Disease, urolithins have negligible potential to inhibit acetylcholinesterase and butyrylcholinesterase enzymes, the validated targets of Alzheimer's Disease. Therefore, within this research, a series of 6H-benzo[c]chromen-6-one, and 7,8,9,10-tetrahydro-benzo[c]chromen-6-one derivatives has been designed, synthesized, and their biological activities were evaluated as potential acetylcholinesterase and butyrylcholinesterase inhibitors. The compounds synthesized exerted comparable activity in comparison to rivastigmine, galantamine, and donepezil both in in vitro and in vivo studies.
authors.affiliation: Nobel Drug Pharmaceutical R&D Center (Nobel-Ilac Ar-Ge Merkezi), Sancaklar Koyu Mevkii, 81100 Duzce, Turkey; Eastern Mediterranean University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Famagusta via Mersin 10, Turkey. Electronic address: ozan.gulcan@emu.edu.tr.
authors.forename: Hayrettin Ozan
authors.initials: HO
authors.lastname: Gulcan
authors.affiliation: Nobel Drug Pharmaceutical R&D Center (Nobel-Ilac Ar-Ge Merkezi), Sancaklar Koyu Mevkii, 81100 Duzce, Turkey.
authors.forename: Serdar
authors.initials: S
authors.lastname: Unlu
authors.affiliation: Nobel Drug Pharmaceutical R&D Center (Nobel-Ilac Ar-Ge Merkezi), Sancaklar Koyu Mevkii, 81100 Duzce, Turkey.
authors.forename: Ilker
authors.initials: I
authors.lastname: Esiringu
authors.affiliation: Nobel Drug Pharmaceutical R&D Center (Nobel-Ilac Ar-Ge Merkezi), Sancaklar Koyu Mevkii, 81100 Duzce, Turkey.
authors.forename: Tugba
authors.initials: T
authors.lastname: Ercetin
authors.affiliation: Nobel Drug Pharmaceutical R&D Center (Nobel-Ilac Ar-Ge Merkezi), Sancaklar Koyu Mevkii, 81100 Duzce, Turkey.
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Sahin
authors.affiliation: Nobel Drug Pharmaceutical R&D Center (Nobel-Ilac Ar-Ge Merkezi), Sancaklar Koyu Mevkii, 81100 Duzce, Turkey.
authors.forename: Demet
authors.initials: D
authors.lastname: Oz
authors.affiliation: Nobel Drug Pharmaceutical R&D Center (Nobel-Ilac Ar-Ge Merkezi), Sancaklar Koyu Mevkii, 81100 Duzce, Turkey; Eastern Mediterranean University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Famagusta via Mersin 10, Turkey.
authors.forename: Mustafa Fethi
authors.initials: MF
authors.lastname: Sahin
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D001578:Benzopyrans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002091:Butyrylcholinesterase / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D015394:Molecular Structure; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C000596410:6H-benzo(c)chromen-6-one; C000596411:7,8,9,10-tetrahydro-benzo(c)chromen-6-one; D001578:Benzopyrans; D002800:Cholinesterase Inhibitors; D011994:Recombinant Proteins; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase
keywords: 6H-Benzo[c]chromen-6-ones; Acetylcholinesterase; Alzheimer’s Disease; Butyrylcholinesterase; Passive avoidance test