Actas de congresos
Qsar Study Of β-lactam Antibiotic Efflux By The Bacterial Multidrug Resistance Pump Acrb
Registro en:
Journal Of Chemometrics. , v. 18, n. 5, p. 242 - 252, 2004.
8869383
10.1002/cem.867
2-s2.0-4444223842
Autor
Ferreira M.M.C.
Kiralj R.
Institución
Resumen
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 β-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 β-lactams with nitrogen- and sulfur-rich substituents. Among the most important β-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. β-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 © 2004 John Wiley & Sons, Ltd. 18 5 242 252 Van Bambeke, F., Balzi, F., Tulkens, P.M., Antibiotics efflux pumps (2002) Biochem. Pharmac., 60, pp. 457-470 Nikaido, H., Multidrug efflux pumps of gram-negative bacteria (1996) J. Bacteriol., 178, pp. 5853-5859 Paulsen, I.T., Brown, M.H., Skurray, R.A., Proton-dependent multidrug efflux system (1996) Microbiol. Rev., 60, pp. 575-608 Sulavik, M., Houseweart, C., Cramer, C., Jiwani, N., Murgolo, N., Greene, J., Di Domenico, B., Shimer, G., Antibiotic susceptibility of Escherichia coli strains lacking multidrug efflux pump genes (2001) Antimicrob. Agents Chemother., 45, pp. 1126-1136 Giraud, E., Cloekaert, A., Kerboeuf, D., Chaslus-Dancla, E., Evidence for active efflux as the primary mechanism of resistance to ciprofloxacin in Salmonella enterica serovar typhimurium (2000) Antimicrob. Agents Chemother., 44, pp. 1223-1228 Okusu, H., Ma, D., Nikaido, H., AcrAB efflux pump plays a major role in the antibiotic resistance phenotype of Escherichia coli multiple-antibiotic-resistance (mar) mutants (1996) J. Bacteriol., 178, pp. 306-308 Zgurskaya, H.I., Nikaido, H., Bypassing the periplasm: Reconstitution of the AcrAB multidrug efflux pump of Escherichia coli (1999) Proc. Natl Acad. Sci. USA, 96, pp. 7190-7195 Helling, R.B., Janes, B.K., Kimball, H., Tran, T., Budesmann, M., Check, P., Phelan, D., Miller, C., Toxic waste disposal in Escherichia coli (2002) J. Bacteriol., 184, pp. 3699-3703 Nikaido, H., Basina, M., Nguyen, V., Rosenberg, E.Y., Multidrug efflux pump AcrB of Salmonella typhimurium exctretes only those β-lactam antibiotics containing lipophilic side chains (1998) J. Bacteriol., 180, pp. 4686-4692 Sanchez, L., Pan, W., Vinas, M., Nikaido, H., The acrAB homolog of Hamemophilus influenzae codes for a functional multidrug efflux pump (1997) J. Bacteriol., 179, pp. 6855-6857 Aono, R., Tsukagoshi, N., Yamamoto, M., Involvement of outer membrane protein TolC, a possible member of the mar-sox regulon, in maintenance and improvement of organic solvent tolerance of Escherichia coli K12 (1998) J. Bacteriol., 180, pp. 938-944 Thanassi, D.G., Cheng, L.W., Nikaido, H., Active efflux of bile salts by Escherichia coli (1997) J. Bacteriol., 179, pp. 2512-2518 White, D.G., Goldman, J.D., Demple, B., Levy, S.B., Role of the acrAB locus in organic solvent tolerance mediated by expression of marA, soxS, or robA in Escherichia coli (1997) J. Bacteriol., 179, pp. 6122-6126 Murakami, S., Nakashima, R., Yamashita, E., Yamaguchi, A., Crystal structure of bacterial multidrug efflux transporter AcrB (2002) Nature, 419, pp. 587-593 Pos, K.M., Diederichs, K., Purification, crystallization and preliminary diffraction studies of AcrB, an inner-membrane multidrug efflux protein (2002) Acta Cryst., D58, pp. 1865-1867 Yu, E.W., McDermott, G., Zgurskaya, H.I., Nikaido, H., Koshland Jr., D.E., Structural basis of multiple drug-binding capacity of the AcrB multidrug efflux pump (2003) Science, 300, pp. 976-980 Cristopher, A.E., Nikaido, H., 3D structure of AcrB: The archetypal multidrug efflux transporter of Escherichia coli likely captures substrates from periplasm (2003) Drug Resist. Updates, 6, pp. 9-13 Koronakis, V., Sharff, A., Koronakis, E., Luisi, B., Hughes, C., Crystal structure of the bacterial membrane protein TolC central to multidrug efflux and protein export (2000) Nature, 405, pp. 914-919 Thanabalu, T., Koronakis, E., Hughes, C., Koronakis, V., Substrates-induced assembly of a contiguous channel from protein export from E. coli: Reversible bridging for an inner-membrane translocase to an outer membrane exit pore (1998) EMBO J., 17, pp. 6487-6496 Dinh, T., Paulsen, I.T., Saier Jr., M.H., A family of extracytoplasmic proteins that allow transport of large molecules across the outer membranes of gram-negative bacteria (1994) J. Bacteriol., 176, pp. 3825-3831 Avila-Sakar, A.J., Misaghi, S., Wilson-Kubalek, E.M., Downing, K.H., Zgurskaya, H., Nikaido, H., Nogales, E., Lipid-layer crystallization and preliminary three-dimensional structural analysis of AcrA, the periplasmic component of a bacterial multidrug efflux pump (2001) J. Struct. Biol., 136, pp. 81-88 Ferreira, M.M.C., Multivariate QSAR (2002) J. Braz. Chem. Soc., 13, pp. 742-753 Alves, C.N., Pinheiro, J.C., Camargo, A.J., Ferreira, M.M.C., Da Silva, A.B.F., A structure activity relationship study of HEPT-analog compounds with anti-HIV activity (2000) Theochem. J. Mol. Struct., 530, pp. 39-47 Bruni, A.T., Ferreira, M.M.C., Omeprazole and analogue compounds: A QSAR study of activity against Helicobacter pylori using theoretical descriptors (2002) J. Chemometrics, 16, pp. 510-520 Kiralj, R., Ferreira, M.M.C., A priori molecular descriptors in QSAR: A case of HIV-1 protease inhibitors. I. The chemometric approach (2003) J. Mol. Graph. Mod., 21, pp. 435-448 Kiralj, R., Ferreira, M.M.C., A priori molecular descriptors in QSAR: A case of HIV-1 protease inhibitors. II. Molecular graphics and modeling (2003) J. Mol. Graph. Mod., 21, pp. 499-515 Kiralj, R., Ferreira, M.M.C., QSAR of progestogens: Use of a priori and computed molecular descriptors and molecular graphics (2003) QSAR Combin. Sci., 22, pp. 430-448 Kiralj, R., Ferreira, M.M.C., Molecular graphics-structural and molecular graphics descriptors in a QSAR study of 17-α-acetoxyprogesterones (2003) J. Braz. Chem. Soc., 14, pp. 20-26 Pinheiro, J.C., Kiralj, R., Ferreira, M.M.C., Romero, O.A.S., Artemisinin derivatives with antimalarial activity against Plasmodium falciparum designed with the aid of quantum chemical and partial least squares methods (2003) QSAR Combin. Sci.., 22, pp. 830-842 Subramanian, S., Ferreira, M.M.C., Trsic, M., A Structure-activity relationship study of lapachol and some derivatives of 1,4-naphthoquinone against carcinosarcoma Walker 256 (1998) Struct. Chem., 9, pp. 47-57 Pinheiro, J.C., Ferreira, M.M.C., Romero, O.A.S., Antimalarial activity of dihydroartemisnin derivatives against P. falciparum resistant to mefloquine: A quantum chemical and multivariate study (2001) Theochem. J. Mol. Struct., 572, pp. 35-44 Vendrame, R., Ferreira, M.M.C., Collins, C.H., Takahata, Y., Structure-activity relationships (SAR) of contraceptive progestogens studied with four different methods using calculated physicochemical parameters (2002) J. Mol. Graph. Mod., 20, pp. 345-358 Geladi, P., Kowalski, B.R., Partial least squares regression - A tutorial (1986) Anal. Chim. Acta, 185, pp. 1-17 Martens, H., Naes, T., (1989) Multivariate Calibration (2nd Edn., , Wiley: New York Beebe, K.R., Pell, R., Seasholtz, M.B., (1998) Chemometrics: A Practical Guide, , Wiley: New York Ferreira, M.M.C., Antunes, A.M., Melo, M.S., Volpe, P.L.O., Chemometrics I: Multivariate calibration, a tutorial (1999) Quím. Nova, 22, pp. 724-731 (2001) PC Spartan Pro 1.0.5, , Wavefunction: Irvine, CA Dobashi, A., 3D Pharmaceutical Structure Database, , www.ps.toyaku.ac.jp/dobashi/3dpsd/index.htm, Department of Structural Organic Chemistry, Tokyo University of Pharmacy and Life Science: Tokyo (2002) The Cambridge Structural Database, , (November Release). Cambridge Crystallographic Data Centre, University of Cambridge: Cambridge Stewart, J.J.P., Optimization of parameters for semiempirical methods. 1. Method (1989) J. Comp. Chem., 10, pp. 209-220 Interactive Analysis Log P and Log W Predictors Website, , www.logp.com, Interactive Analysis: Bedford, MA ALOGPS 2.1, , http://146.107.217.178/lab/alogps/, Virtual Computational Chemistry Laboratory Koltun, W.L., Precision space-filling atomic models (1965) Biopolymers, 3, pp. 665-679 Lobanov, V.S., (1996) MOPAC 6.0 for Microsoft Windows, , University of Florida, Miami, FL (2001) Matlab 6.1.0.450 Release 12.1, , Math Works: Natick, MA (2001) Pirouette 3.01, , Infometrix: Woodinville, WA Abraham, D.J., Kellog, G.E., Hydrophobic fields (2000) 3D QSAR in Drug Design: Theory, Methods and Applications, pp. 506-522. , Kubinyi H (ed.). Kluwer/Escom: Dordrecht Lien, E.J., (1987) SAR Side Effects and Drug Design, pp. 41-162. , Marcel Dekker: New York Hansch, C., Steward, A.R., Anderson, S.M., Bentley, D., The parabolic dependence of drug action upon lipophilicity character as revealed by a study of hypnotics (1968) J. Med. Chem., 11, pp. 1-11 Hyde, R.M., Relationships between the biological and physiological properties of series of compounds (1975) J. Med. Chem., 18, pp. 231-233 Cole, J.C., Lommerse, J.P.M., Rowlands, R.S., Taylor, R., Allen, F.H., Use of Cambridge Structural Database to Study Non-covalent interactions: Towards a knowledge base of intermolecular interactions (1998) Structure-based Drug Design: Experimental and Computational Approaches, 352, pp. 113-124. , Codding PW (ed.). NATO ASI Series E: Applied Sciences. Kluwer: Dordrecht Glusker, J.P., Lewis, M., Rossi, M., (1994) Crystal Structure Analysis for Chemists and Biologists, , Chap. 15 and 17. VCH: New York Nishio, M., Hirota, M., Umezawa, Y., (1998) The CH/π Interaction, , Wiley-VCH: New York Scheiner, S., Kar, T., Gu, Y., Strength of the CαH O⋯ hydrogen bond of amino acid residues (2001) J. Biol. Chem., 276, pp. 9832-9837 Protein Data Bank, , www.rcsb.org/index.html Kaiser, K.L.E., Niculescu, S.P., Using probabilistic neural networks to model the toxicity of chemicals to the fat-head minnow (Pimephales promelas): A study based on 865 compounds (1999) Chemosphere, 38, pp. 3237-3245 Van De Waterbeemd, H., El Tayar, N., Carrupt, P.A., Testa, B., Pattern-recognition study of QSAR substituent descriptors (1989) J. Comput-Aid. Molec. Des., 3, pp. 111-132 Dutta, M., Dutta, N.N., Bhattacharyya, K.G., Adsorptive interaction of certain β-lactam antibiotics in aqueous solution: Interpretation by frontier-orbital theory (2000) J. Chem. Eng. Jpn., 33, pp. 303-307 Leon, S., Alemán, C., García-Alvarez, M., Muñoz-Guerra, S., Theoretical study of the conformational and electrostatic properties of C4-monosubstituted 2-azetidinones (1997) Struct. Chem., 8, pp. 39-47