Title:Topological Model for the Search of New Antibacterial Drugs. 158 Theoretical Candidates
VOLUME: 11 ISSUE: 4
Author(s):Jose I. Bueso-Bordils, Pedro A. Alemán, Luis Lahuerta Zamora, Rafael Martín-Algarra, María J. Duart and Gerardo M. Antón-Fos
Affiliation:Department of Pharmacy, Faculty of Health Sciences, CEU Cardenal Herrera University, P.O. Box: 46113, Moncada, Spain.
Keywords:Antibacterial, antibiotics, computational chemistry, linear discriminant analysis, molecular topology, quinolones.
Abstract:In this paper, molecular topology was used to develop a mathematical model capable of
classifying compounds according to their antibacterial activity.
Topological indices were used as structural descriptors and their relation to antibacterial activity was
determined by applying linear discriminant analysis (LDA) on a group of quinolones, widely used
nowadays because of their broad spectrum of activity, well tolerance profile and advantageous
pharmacokinetic properties.
The topological model of activity obtained included two discriminant functions, selected by a combination of various
statistical paremeters such as Fisher-Snedecor F and Wilk’s lambda, and allows the reliable prediction of antibacterial
activity in any organic compound. After a virtual pharmacological screening on a library of 6375 compounds, the model
has selected 263 as active compounds, from which 40% have proven antibacterial activity.
The results obtained clearly reveal the high efficiency of molecular topology for the prediction of pharmacological
activities. These models are very helpful in the discovery of new applications of natural and synthetic molecules with
different chemical or biological properties. Therefore, we finally present 158 strong candidates to be developed as novel
antibacterials.
