title: Structural aspects of flavonoids as inhibitors of human butyrylcholinesterase.
abstract: Selected flavonoids: galangin, kaempferol, quercetin, myricetin, fisetin, apigenin, luteolin and rutin, reversibly inhibited human butyrylcholinesterase (BChE, EC 3.1.1.8). Inhibition potency of the flavonoids we attributed to their chemical structure, i.e., the number of OH groups and their side on the phenyl ring. The most potent BChE inhibitor among the tested flavonoids was galangin, which showed 12 times higher preference for binding to BChE (7 micromol/L) than to the related enzyme human acetylcholinesterase (AChE, EC 3.1.1.7). Docking study showed that flavonoids bind to the BChE active site by forming multiple hydrogen bonds and pi-pi interactions. The UV-VIS (200-500 nm) absorption spectra of the flavonoid phosphate buffer solution (pH 7.4), with the exception of rutin, revealed time dependant changes indicating precipitation of flavonoids or in the case of myricetin, a change in the chemical structure resulting in a BChE non-inhibiting specie. Selected flavonoids showed no cytotoxic effect on HepG2 and A549 cell lines at concentrations up to 200 micromol/L. Cytotoxicity was observed only for fisetin, apigenin and luteolin in the THP-1 cell line with IC50 of 30, 60 and 70 micromol/L, respectively.
authors.affiliation: Institute for Medical Research and Occupational Health, Ksaverska cesta 2, HR-10000 Zagreb, Croatia.
authors.forename: Maja
authors.initials: M
authors.lastname: Katalinić
authors.forename: Gordana
authors.initials: G
authors.lastname: Rusak
authors.forename: Jelena
authors.initials: J
authors.lastname: Domaćinović Barović
authors.forename: Goran
authors.initials: G
authors.lastname: Sinko
authors.forename: Dubravko
authors.initials: D
authors.lastname: Jelić
authors.forename: Roberto
authors.initials: R
authors.lastname: Antolović
authors.forename: Zrinka
authors.initials: Z
authors.lastname: Kovarik
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D002091:Butyrylcholinesterase / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D045744:Cell Line, Tumor; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D005419:Flavonoids / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D013379:Substrate Specificity
chemical_list: D002800:Cholinesterase Inhibitors; D005419:Flavonoids; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase