| dc.creator | Cho, Sung Jin | |
| dc.creator | Serrano Garcia, Maria Luisa | |
| dc.creator | Bier, Jim | |
| dc.creator | Tropsha, Alexander | |
| dc.date | 2019-01-11T17:49:55Z | |
| dc.date | 2019-01-11T17:49:55Z | |
| dc.date | 2019-01-11 | |
| dc.date.accessioned | 2022-10-28T01:35:34Z | |
| dc.date.available | 2022-10-28T01:35:34Z | |
| dc.identifier | DOI: 10.1021/jm950771r | |
| dc.identifier | http://hdl.handle.net/10872/19557 | |
| dc.identifier.uri | https://repositorioslatinoamericanos.uchile.cl/handle/2250/4952996 | |
| dc.description | The method of comparative molecular field analysis (CoMFA) was used to develop quantitative
structure-activity relationships for physostigmine, 9-amino-1,2,3,4-tetrahydroacridine (THA),
edrophonium (EDR), and other structurally diverse inhibitors of acetylcholinesterase (AChE).
The availability of the crystal structures of enzyme/inhibitor complexes (EDR/AChE, THA/
AChE, and decamethonium (DCM)/AChE) (Harel, M.; et al. Quaternary ligand binding to
aromatic residues in the active-site gorge of acetylcholinesterase. Proc. Natl. Acad. Sci. U.S.A.
1993, 90, 9031-9035) provided information regarding not only the active conformation of the
inhibitors but also the relative mutual orientation of the inhibitors in the active site of the
enzyme. Crystallographic conformations of EDR and THA were used as templates onto which
additional inhibitors were superimposed. The application of cross-validated R2 guided region
selection method, recently developed in this laboratory (Cho, S. J.; Tropsha, A. Cross-Validated
R2 Guided Region Selection for Comparative Molecular Field Analysis (CoMFA): A Simple
Method to Achieve Consistent Results. J. Med. Chem. 1995, 38, 1060-1066), to 60 AChE
inhibitors led to a highly predictive CoMFA model with the q2 of 0.734. | |
| dc.description | PHS Grant MH 40537 and Center Grants
HD03310 and MH33127 M.L.S. acknowledges the support from “Programa de Nuevas Tecnologı´as” CONICIT-Venezuela and CDCH of the Universidad Central de Venezuela
Training Grant. J. Bier appreciates the support from Wellcome Foundation. | |
| dc.language | en_US | |
| dc.relation | J. Med. Chem.;1996, 39, 5064-5071 | |
| dc.subject | comparative molecular field analysis (CoMFA) | |
| dc.subject | QSAR | |
| dc.subject | Acetylcholinesterase Inhibitors | |
| dc.title | Structure-Based Alignment and Comparative Molecular Field Analysis of Acetylcholinesterase Inhibitors | |
| dc.type | Article | |
