Enabling virtual screening of potent and safer antimicrobial agents against noma: Mtk-QSBER model for simultaneous pbkp_rediction of antibacterial activities and ADMET properties

Abstract:

Neglected diseases are infections that thrive mainly among underdeveloped countries, particularly those belonging to regions found in Asia, Africa, and America. One of the most complex diseases is noma, a dangerous health condition characterized by a polymicrobial and opportunistic nature. The search for potent and safer antibacterial agents against this disease is therefore a goal of particular interest. Chemoinformatics can be used to rationalize the discovery of drug candidates, diminishing time and financial resources. However, in the case of noma, there is no in silico model available for its use in the discovery of efficacious antibacterial agents. This work is devoted to report the first mtk-QSBER model, which integrates dissimilar kinds of chemical and biological data. The model was generated with the aim of simultaneously pbkp_redicting activity against bacteria present in noma, and ADMET (absorption, distribution, metabolism, elimination, toxicity) parameters. The mtk-QSBER model was constructed by employing a large and heterogeneous dataset of chemicals and displayed accuracies higher than 90% in both training and pbkp_rediction sets. We confirmed the practical applicability of the model by pbkp_redicting multiple profiles of the investigational antibacterial drug delafloxacin, and the pbkp_redictions converged with the experimental reports. To date, this is the first model focused on the virtual search for desirable anti-noma agents.

Año de publicación:

2015

Keywords:

• antibacterial
• linear discriminant analysis
• NOMA
• ADMET
• Quadratic Indices

Fuente:

scopus