JAC Advance Access published online on November 25, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh014
© 2003 by The British Society for Antimicrobial Chemotherapy
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Original article
1 Unidad de Investigación
de Diseño de Fármacos y Conectividad Molecular,
Departamento de Química Física, Facultad de Farmacia,
Universitat de València, 46100 Burjassot, Valencia;
* Corresponding author. E-mail: jorge.galvez{at}uv.es.
Received 27 March 2003
; revised 25 September 2003
; accepted 3 October 2003
Objectives: In order to select new
drugs and to predict their in vitro activity against Mycobacterium avium complex (MAC), new quantitative
structure-activity relationship (QSAR) models were developed. Methods: The activities against MAC of 29 structurally
heterogeneous drugs were examined by means of linear discriminant
analysis (LDA) and multilinear regression analysis (MLRA) by using
topological indices (TI) as structural descriptors. In
vitro antimycobacterial activities were determined by a broth
microdilution method with 7H9 medium. Results: The topological model obtained successfully
classifies over 80% of compounds as active or inactive; consequently,
it was applied in the search for new molecules active against MAC.
From among the selected candidates demonstrating in
vitro activity, aflatoxin B1, benzalkonium chloride and pentamidine
stand out, with MIC50s between 4 and 32 mg/L. Conclusion: The method described in this work
is able to select molecules active against MAC.
Keywords: MAC, QSAR studies, topological indices
New agents active against Mycobacterium
avium complex selected by molecular topology: a virtual screening
method
2 Institut de Química Computacional, Universitat
de Girona, 17071 Girona;
3 Departamento
de Microbiología, Facultad de Medicina y Odontología, Universitat
de València, Av. Blasco Ibáñez 15, 46010
Valencia, Spain
4 Unidad de Investigación
de Diseño de Fármacos y Conectividad Molecular,
Departamento de Química Física, Facultad de Farmacia,
Universitat de València, 46100 Burjassot, Valencia; Departamento
de Microbiología, Facultad de Medicina y Odontología, Universitat
de València, Av. Blasco Ibáñez 15, 46010
Valencia, Spain
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