Tree-Based QSAR Model for Drug Repurposing in the Discovery of New Antibacterial Compounds Against Escherichia coli.

Pharmaceuticals

J. Ignacio Bueso-Bordils¹  M. Teresa Pérez-Gracia¹  Gerardo M. Anton-Fos¹  Pedro A. Alemán-López¹  Antonio Falcó²  Beatriz Suay-Garcia² 

[1] Departamento de Farmacia Universidad Cardenal Herrera-CEU, CEU Universities, Alfara del Patriarca, 46115 Valencia, Spain;Departamento de Matemáticas, Física y Ciencias Tecnológicas, Universidad Cardenal Herrera-CEU, CEU Universities, Alfara del Patriarca, 46115 Valencia, Spain;

关键词: drug repurposing;    QSAR;    antibiotics;    drug development;    Escherichia coli;   

DOI  :  10.3390/ph13120431

来源: DOAJ

【 摘 要 】

Drug repurposing appears as an increasing popular tool in the search of new treatment options against bacteria. In this paper, a tree-based classification method using Linear Discriminant Analysis (LDA) and discrete indexes was used to create a QSAR (Quantitative Structure-Activity Relationship) model to predict antibacterial activity against Escherichia coli. The model consists on a hierarchical decision tree in which a discrete index is used to divide compounds into groups according to their values for said index in order to construct probability spaces. The second step consists in the calculation of a discriminant function which determines the prediction of the model. The model was used to screen the DrugBank database, identifying 134 drugs as possible antibacterial candidates. Out of these 134 drugs, 8 were antibacterial drugs, 67 were drugs approved for different pathologies and 55 were drugs in experimental stages. This methodology has proven to be a viable alternative to the traditional methods used to obtain prediction models based on LDA and its application provides interesting new drug candidates to be studied as repurposed antibacterial treatments. Furthermore, the topological indexes Nclass and Numhba have proven to have the ability to group active compounds effectively, which suggests a close relationship between them and the antibacterial activity of compounds against E. coli.

【 授权许可】

Unknown