title: Rapid identification of antibacterial agents effective against Staphylococcus aureus using small-molecule macroarrays.
abstract: There is an urgent, global need for the development of new antibacterial agents. We have applied the small-molecule macroarray approach to the synthesis and screening of antibacterial compounds active against the Gram-positive pathogen Staphylococcus aureus. Several macroarrays of 1,3-diphenyl-2-propen-1-ones (chalcones), cyanopyridines, and pyrimidines were synthesized on a planar cellulose support system on the order of days. This support system was found to be highly compatible with antibacterial assay formats, including disk-diffusion and agar-overlay visualization methods. Further, sufficient compound was isolated from each spot of the macroarray for both compound characterization and minimum inhibitory concentration (MIC) estimation. Analysis of the small-molecule macroarrays in these assays uncovered a set of antibacterial agents with in vitro MIC values against methicillin-resistant S. aureus comparable to certain antibacterial drugs in use today.
authors.affiliation: Department of Chemistry, University of Wisconsin, Madison, 1101 University Avenue, Madison, WI 53706, USA.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Bowman
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: O'Neill
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Stringer
authors.forename: Helen E
authors.initials: HE
authors.lastname: Blackwell
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000302:isolation & purification* / Q000494:pharmacology; D047188:Chalcones / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical; D015195:Drug Design; D024881:Drug Resistance, Bacterial; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests / Q000379:methods; D011725:Pyridines / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D047188:Chalcones; D011725:Pyridines; D011743:Pyrimidines