Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/58517
Type: Artigo de periódico
Title: QSAR study of beta-lactam antibiotic efflux by the bacterial multidrug resistance pump AcrB
Author: Ferreira, MMC
Kiralj, R
Abstract: AcrAB-TolC is the most important efflux pump system of Gram-negative bacteria, responsible for their resistance to lipophilic and amphilic drugs. In this work, HCA-PCA studies were performed to investigate the relationship between efflux activities (negative logarithm of minial inhibitor concentration, pMIC) of three strains of S. thypimurium with respect to beta-lactams, and to analyze the relationship between lipophilicity parameters calculated by different methods. The analyses demonstrate that pMICs strongly depend on properties of both bacterial strains and drug molecules, and that lipophilicity parameters do not necessarily contain the same information about the drugs. QSAR studies have shown that the calculated lipophilicities, in some cases, are non linearly related to the pMICs originated by active AcrAB-TolC bacterial pumps, due to the existence of beta-lactams with nitrogen- and sulfur-rich substituents. Among the most important beta-lactam molecular properties quantitatively related to pMICs are lipophilicity and electronic and hydrogen-bonding properties. Parameters describing these properties were included in the QSAR study to obtain parsimonius regression models for MICs. beta-Lactams were classified as good, moderately good and poor AcrAB-TolC substrates. Their stereoelectronic molecular properties, especially the Y-component of the molecular dipole moment and hydrogen binding properties, reflected this classification. Copyright (C) 2004 John Wiley Sons, Ltd.
Subject: AcrB multidrug resistance efflux pump
beta-lactam antibiotics
QSAR
PLS
Country: Inglaterra
Editor: John Wiley & Sons Ltd
Rights: fechado
Identifier DOI: 10.1002/cem.867
Date Issue: 2004
Appears in Collections:Unicamp - Artigos e Outros Documentos

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