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 H-1 and C-13 NMR spectra of la and Ib was performed by monodimensional and homo- and hetero-correlated two-dimensional NMR experiments. This study was undertaken to elucidate the interaction modes between AChE and la and lb 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 la 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 5412 M-1 for la and1b, respectively. (C) 2007 Elsevier Inc. All rights reserved.
Tacrine derivatives-acetylcholinesterase interaction: H-1 NMR relaxation study / Delfini, Maurizio; DI COCCO, Maria Enrica; Piccioni, Fabiana; F., Porcelli; A., Borioni; A., Rodomonte; M. R., Del Giudice. - In: BIOORGANIC CHEMISTRY. - ISSN 0045-2068. - STAMPA. - 35:3(2007), pp. 243-257. [10.1016/j.bioorg.2007.01.001]
Tacrine derivatives-acetylcholinesterase interaction: H-1 NMR relaxation study
DELFINI, Maurizio;DI COCCO, Maria Enrica;PICCIONI, Fabiana;
2007
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 H-1 and C-13 NMR spectra of la and Ib was performed by monodimensional and homo- and hetero-correlated two-dimensional NMR experiments. This study was undertaken to elucidate the interaction modes between AChE and la and lb 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 la 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 5412 M-1 for la and1b, respectively. (C) 2007 Elsevier Inc. All rights reserved.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
