title: Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of tricyclic oxazolidinones as antibacterial agents.
abstract: Oxazolidinones exemplified by eprezolid and linezolid are a new class of antibacterials that are active against Gram positive and anaerobic bacteria including methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE) and vancomycin resistant enterococci (VRE). In an effort to have a better antibacterial agent in the oxazolidinone class, we have performed three-dimensional quantitative structure-activity relationship (3D-QSAR) studies for a series of tricyclic oxazolidinones. 3D-QSAR studies were performed using the Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) procedures. These studies were performed using 42 compounds; the QSAR model was developed using a training set of 33 compounds. The predictive ability of the QSAR model was assessed using a test set of 9 compounds. The predictive 3D-QSAR models have conventional r(2) values of 0.975 and 0.940 for CoMFA and CoMSIA respectively; similarly, cross-validated coefficient q(2) values of 0.523 and 0.557 for CoMFA and CoMSIA, respectively, were obtained. The CoMFA 3D-QSAR model performed better than the CoMSIA model.
authors.affiliation: Department of Molecular Modeling and Drug Design, Dr. Reddy's Laboratories Ltd., Discovery Research, Bollaram Road, Miyapur, Hyderabad 500 050, India. gopalakrishnanb@drreddys.com
authors.forename: Bulusu
authors.initials: B
authors.lastname: Gopalakrishnan
authors.forename: Akash
authors.initials: A
authors.lastname: Khandelwal
authors.forename: Shaikh Abdul
authors.initials: SA
authors.lastname: Rajjak
authors.forename: Natesan
authors.initials: N
authors.lastname: Selvakumar
authors.forename: Jagattaran
authors.initials: J
authors.lastname: Das
authors.forename: Sanjay
authors.initials: S
authors.lastname: Trehan
authors.forename: Javed
authors.initials: J
authors.lastname: Iqbal
authors.forename: Magadi Sitaram
authors.initials: MS
authors.lastname: Kumar
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology*; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D023303:Oxazolidinones / Q000737:chemistry* / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D013211:Staphylococcus aureus / Q000187:drug effects; D055672:Static Electricity
chemical_list: D000890:Anti-Infective Agents; D023303:Oxazolidinones