title: Antibacterial activity of a series of N2,N4-disubstituted quinazoline-2,4-diamines.
abstract: A series of N(2),N(4)-disubstituted quinazoline-2,4-diamines has been synthesized and tested against multidrug resistant Staphylococcus aureus. A structure-activity and structure-property relationship study was conducted to identify new hit compounds. This study led to the identification of N(2),N(4)-disubstituted quinazoline-2,4-diamines with minimum inhibitory concentrations (MICs) in the low micromolar range in addition to favorable physicochemical properties. Testing of biological activity revealed limited potential for resistance to these agents, low toxicity, and highly effective in vivo activity, even with low dosing regimens. Collectively, these characteristics make this compound series a suitable platform for future development of antibacterial agents.
authors.affiliation: Department of Chemistry, University of South Florida , 4202 East Fowler Avenue, CHE 205, Tampa, Florida 33620, United States.
authors.forename: Kurt S
authors.initials: KS
authors.lastname: Van Horn
authors.forename: Whittney N
authors.initials: WN
authors.lastname: Burda
authors.forename: Renee
authors.initials: R
authors.lastname: Fleeman
authors.forename: Lindsey N
authors.initials: LN
authors.lastname: Shaw
authors.forename: Roman
authors.initials: R
authors.lastname: Manetsch
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D003959:Diamines / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007814:Larva / Q000254:growth & development / Q000382:microbiology; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010538:Peritonitis / Q000188:drug therapy* / Q000382:microbiology; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology*; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D003959:Diamines; D011799:Quinazolines