Rapid identification of antibacterial agents effective against Staphylococcus aureus using small-molecule macroarrays.
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.
Bowman
Matthew D
MD
Department of Chemistry, University of Wisconsin, Madison, 1101 University Avenue, Madison, WI 53706, USA.
O'Neill
Jennifer C
JC
Stringer
Joseph R
JR
Blackwell
Helen E
HE
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*
D000900:Anti-Bacterial Agents; D047188:Chalcones; D011725:Pyridines; D011743:Pyrimidines