| Molecular determinants of MAO selectivity in a series of indolylmethylamine derivatives: biological activities, 3D-QSAR/CoMFA analysis, and computational simulation of ligand recognition. | |
| | |
MedLine Citation:
|
PMID: 10794685 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
A series of indolylmethylamine derivatives were assayed toward MAO-A and MAO-B inhibition. The K(i) values of these compounds are in the range from 0.8 to >10(6) nM for MAO-A or from 0.75 to 476000 nM for MAO-B. The most selective MAO-A or MAO-B inhibitors elicit a ratio of K(i) in the order of 1500 or 1000, respectively. Comparison of MAO-A and MAO-B CoMFA models showed that both the steric and electrostatic properties at the 5 position of the indole ring are determinant for MAO selectivity. Computational simulations of the complex between this part of the ligand and Phe-208 of MAO-A or Ile-199 of MAO-B, experimentally identified as responsible for substrate selectivity, allowed us to further characterize the nature of these enzyme-inhibitor interactions. |
| | |
Authors:
|
J A Morón; M Campillo; V Perez; M Unzeta; L Pardo |
Related Documents
:
|
10864435 - Reversible sodium dodecyl sulfate activation of latent peach polyphenol oxidase by cycl... 18230605 - Betaine-homocysteine s-methyltransferase-2 is an s-methylmethionine-homocysteine methyl... 3110375 - Turnover of brain monoamine oxidase measured in vivo by positron emission tomography us... 16917825 - Distinct structure and activity of monoamine oxidase in the brain of zebrafish (danio r... 9773485 - Activity of cellulolytic enzymes in the contents of reticulorumen and caecocolon of roe... 20851885 - Mutational analysis of saccharomyces cerevisiae erf2 reveals a two-step reaction mechan... |
Publication Detail:
|
Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Journal of medicinal chemistry Volume: 43 ISSN: 0022-2623 ISO Abbreviation: J. Med. Chem. Publication Date: 2000 May |
Date Detail:
|
Created Date: 2000-06-29 Completed Date: 2000-06-29 Revised Date: 2006-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 9716531 Medline TA: J Med Chem Country: UNITED STATES |
Other Details:
|
Languages: eng Pagination: 1684-91 Citation Subset: IM |
Affiliation:
|
Laboratori de Medicina Computacional, Unitat de Bioestadistica, Facultat de Medicina, and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Amines
/
chemical synthesis* Animals Computer Simulation Indoles / chemical synthesis*, pharmacology Isoenzymes / chemistry, genetics Isoleucine / chemistry Kinetics Ligands Male Mitochondria, Liver / drug effects, enzymology Models, Molecular Monoamine Oxidase / chemistry*, genetics Monoamine Oxidase Inhibitors / chemical synthesis*, chemistry, pharmacology Phenylalanine / chemistry Rats Rats, Sprague-Dawley Structure-Activity Relationship |
| Chemical | |
Reg. No./Substance:
|
0/Amines; 0/Indoles; 0/Isoenzymes; 0/Ligands; 0/Monoamine Oxidase Inhibitors; 63-91-2/Phenylalanine; 73-32-5/Isoleucine; EC 1.4.3.4/Monoamine Oxidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Substituted benzamide inhibitors of human rhinovirus 3C protease: structure-based design, synthesis,...
Next Document: Probing the conformation of the sugar transport inhibitor phlorizin by 2D-NMR, molecular dynamics st...