title: Tacrine derivatives-acetylcholinesterase interaction: 1H NMR relaxation study.
abstract: Two acetylcholinesterase (AChE) inhibitors structurally related to Tacrine, 6-methoxytacrine (1a) and 9-heptylamino-6-methoxytacrine (1b), and their interaction with Electrophorus Electricus AChE were investigated. The complete assignment of the 1H and 13C NMR spectra of 1a and 1b was performed by mono-dimensional and homo- and hetero-correlated two-dimensional NMR experiments. This study was undertaken to elucidate the interaction modes between AChE and 1a and 1b in solution, using NMR. The interaction between the two inhibitors and AChE was studied by the analysis of the motional parameters non-selective and selective spin-lattice relaxation times, thereby allowing the motional state of 1a and 1b, both free and bound with AChE, to be defined. The relaxation data pointed out the ligands molecular moiety most involved in the binding with AChE. The relevant ligand/enzyme interaction constants were also evaluated for both compounds and resulted to be 859 and 5412M(-1) for 1a and1b, respectively.
authors.affiliation: Dipartimento di Chimica, Università degli Studi La Sapienza, piazzale Aldo Moro, 5 - 00185 Roma, Italy. maurizio.delfini@uniroma1.it
authors.forename: Maurizio
authors.initials: M
authors.lastname: Delfini
authors.forename: Maria Enrica
authors.initials: ME
authors.lastname: Di Cocco
authors.forename: Fabiana
authors.initials: F
authors.lastname: Piccioni
authors.forename: Fernando
authors.initials: F
authors.lastname: Porcelli
authors.forename: Anna
authors.initials: A
authors.lastname: Borioni
authors.forename: Andrea
authors.initials: A
authors.lastname: Rodomonte
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Del Giudice
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry* / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy / Q000379:methods* / Q000592:standards; D015394:Molecular Structure; D011522:Protons; D012015:Reference Standards; D012680:Sensitivity and Specificity; D013329:Structure-Activity Relationship; D013619:Tacrine / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D008024:Ligands; D011522:Protons; D013619:Tacrine; D000110:Acetylcholinesterase