title: Computer-aided design of novel antibacterial 3-hydroxypyridine-4-ones: application of QSAR methods based on the MOLMAP approach.
abstract: 3-Hydroxypyridine-4-one derivatives have shown good inhibitory activity against bacterial strains. In this work we report the application of MOLMAP descriptors based on empirical physicochemical properties with genetic algorithm partial least squares (GA-PLS) and counter propagation artificial neural networks (CP-ANN) methods to propose some novel 3-hydroxypyridine-4-one derivatives with improved antibacterial activity against Staphylococcus aureus. A large collection of 302 novel derivatives of this chemical scaffold was selected for this purpose. The activity classes of these compounds were determined using the two quantitative structure activity relationships models. To evaluate the predictability and accuracy of the obtained models, nineteen compounds belonging to all three activity classes were prepared and the activity of them was determined against S. aureus. Comparing the experimental results and the predicted activity classes revealed the accuracy of the obtained models. Seventeen of the nineteen synthesized molecules were correctly predicted by GA-PLS model according to the antimicrobial evaluation method. Molecules 5f and 5h proved to be moderately active and active experimentally, but were predicted as inactive and moderately active compounds, respectively by this model. The CP-ANN based prediction was correct for sixteen out of the nineteen synthesized molecules. 5a, 5h and 5q were moderately active and active based on the antimicrobial assays, but they were introduced as members of inactive, moderately active and inactive classes of compounds, respectively according to CP-ANN model.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences and Isfahan Pharmaceutical Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Razieh
authors.initials: R
authors.lastname: Sabet
authors.forename: Afshin
authors.initials: A
authors.lastname: Fassihi
authors.forename: Bahram
authors.initials: B
authors.lastname: Hemmateenejad
authors.forename: Lotfollah
authors.initials: L
authors.lastname: Saghaei
authors.forename: Ramin
authors.initials: R
authors.lastname: Miri
authors.forename: Maryam
authors.initials: M
authors.lastname: Gholami
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D017076:Computer-Aided Design; D008826:Microbial Sensitivity Tests; D011728:Pyridones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D011728:Pyridones; C020366:3-hydroxy-4-pyridone