title: Novel benzofuroxan derivatives against multidrug-resistant Staphylococcus aureus strains: design using Topliss' decision tree, synthesis and biological assay.
abstract: The aim of this study was the design of a set of benzofuroxan derivatives as antimicrobial agents exploring the physicochemical properties of the related substituents. Topliss' decision tree approach was applied to select the substituent groups. Hierarchical cluster analysis was also performed to emphasize natural clusters and patterns. The compounds were obtained using two synthetic approaches for reducing the synthetic steps as well as improving the yield. The minimal inhibitory concentration method was employed to evaluate the activity against multidrug-resistant Staphylococcus aureus strains. The most active compound was 4-nitro-3-(trifluoromethyl)[N'-(benzofuroxan-5-yl)methylene]benzhydrazide (MIC range 12.7-11.4 μg/mL), pointing out that the antimicrobial activity was indeed influenced by the hydrophobic and electron-withdrawing property of the substituent groups 3-CF(3) and 4-NO(2), respectively.
authors.affiliation: Departamento de Tecnologia Bioquímico Farmacêutica, Faculdade de Farmácia, Universidade de São Paulo, São Paulo, SP 05508-900, Brazil. sdjorge@usp.br
authors.forename: Salomão Dória
authors.initials: SD
authors.lastname: Jorge
authors.forename: Fanny
authors.initials: F
authors.lastname: Palace-Berl
authors.forename: Andrea
authors.initials: A
authors.lastname: Masunari
authors.forename: Cléber André
authors.initials: CA
authors.lastname: Cechinel
authors.forename: Marina
authors.initials: M
authors.lastname: Ishii
authors.forename: Kerly Fernanda Mesquita
authors.initials: KF
authors.lastname: Pasqualoto
authors.forename: Leoberto Costa
authors.initials: LC
authors.lastname: Tavares
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D001583:Benzoxazoles / Q000737:chemistry*; D003663:Decision Trees; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D012680:Sensitivity and Specificity; D012984:Software; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000378:metabolism; D013329:Structure-Activity Relationship; D010069:Oxadiazoles
chemical_list: D000900:Anti-Bacterial Agents; D001583:Benzoxazoles; C014354:benzofuroxan; D010069:Oxadiazoles