title: Enabling virtual screening of potent and safer antimicrobial agents against noma: mtk-QSBER model for simultaneous prediction 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 predicting 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 prediction sets. We confirmed the practical applicability of the model by predicting multiple profiles of the investigational antibacterial drug delafloxacin, and the predictions converged with the experimental reports. To date, this is the first model focused on the virtual search for desirable anti-noma agents.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Speck-Planche
authors.affiliation: REQUIMTE/Department of Chemistry and Biochemistry, University of Porto, 4169-007 Porto, Portugal. alejspivanovich@gmail.com.
authors.forename: M N D S
authors.initials: MN
authors.lastname: Cordeiro
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000493:pharmacokinetics; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D019540:Area Under Curve; D001441:Bacteroides fragilis / Q000187:drug effects; D001682:Biological Availability; D003198:Computer Simulation; D016002:Discriminant Analysis; D024841:Fluoroquinolones / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D005673:Fusobacterium / Q000187:drug effects; D006207:Half-Life; D006801:Humans; D008826:Microbial Sensitivity Tests; D009625:Noma / Q000188:drug therapy*; D010462:Peptostreptococcus / Q000187:drug effects; D021281:Quantitative Structure-Activity Relationship; D012372:ROC Curve; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D024841:Fluoroquinolones; C477891:delafloxacin