Amphiphilic polymethacrylate derivatives as antimicrobial agents.
We have investigated the structure-activity relationship of cationic amphiphilic polymethacrylate derivatives in antimicrobial and hemolytic assays. The polymers were prepared by radical copolymerizations of N-(tert-butoxycarbonyl)aminoethyl methacrylate and butyl methacrylate in the presence of methyl 3-mercaptopropionate as a chain transfer agent to give precursor polymers protected with a tert-butoxycarbonyl (Boc) group. Subsequent treatment of the Boc-protected polymers with TFA affords the desired cationic random copolymers. We examined antimicrobial and hemolytic activities of a series of polymers having a wide range of mole percentage of butyl groups (0-60%) in three different molecular weight (MW) ranges. The smallest polymers (MW < 2000) showed the lowest MIC and reduced hemolytic activity compared to that of the higher MW ones. In addition, polymers containing a high percentage of butyl groups are less selective for bacterial cells than their less hydrophobic counterparts.
Kuroda
Kenichi
K
Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
DeGrado
William F
WF
D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008826:Microbial Sensitivity Tests; D011109:Polymethacrylic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000890:Anti-Infective Agents; D011109:Polymethacrylic Acids