Researchers at University of Southern California, Department of Pharmacology release new data on drug resistance
2007 NOV 19 -- New investigation results, 'Development of Tyrocidine A analogues with improved antibacterial activity,' are detailed in a study published in Bioorganic & Medicinal Chemistry. "The development of new antibacterial therapeutic agents capable of halting microbial resistance is a chief pursuit in clinical medicine. Classes of antibiotics that target and destroy bacterial membranes are attractive due to the decreased likelihood that bacteria will be able to generate resistance to this mechanism," researchers in the United States report. "The amphipathic cyclic decapeptide, Tyrocidine A, is a model for this class of antibiotics. Tyrocidine A is composed of a hydrophobic and a hydrophilic face, allowing for insertion into bacterial membranes, creating porous channels and destroying membrane integrity. We have used a combination of molecular modeling and solid phase synthesis to prepare Tyrocidine A and analogues 1-8. The minimum inhibitory concentrations (MICs) of these compounds were determined for a host of gram positive species and E. coli as a representative gram negative bacterium. Analogues 2 and 5 demonstrated moderate 2-to 8-fold increases in antibacterial activity over the parent Tyrocidine A for a variety of pathogenic microbes (best MICs for E. coli 32 microg/mL and 2 microg/mL for most gram positives). Examination of the structure-activity relationship between the analogues demonstrated a preference for increased amphipathicity but did not show a clear preference for increasing hydrophilicity versus hydrophobicity in improving antibacterial activity," wrote M.A. Marques and colleagues, University of Southern California, Department of Pharmacology. The researchers concluded: "Of note, movement of positively charged lysine residues or neutral pentafluorophenyl residues to different positions within the cyclopeptide ring system demonstrated improvements in antibacterial activity." Marques and colleagues published their study in Bioorganic & Medicinal Chemistry (Development of Tyrocidine A analogues with improved antibacterial activity. Bioorganic & Medicinal Chemistry, 2007;15(21):6667-77). For additional information, contact M.A. Marques, University of Southern California, Dept. of Pharmacology, Los Angeles, CA 90089 USA.. Publisher contact information for the journal Bioorganic & Medicinal Chemistry is: Pergamon-Elsevier Science Ltd., the Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, England. Keywords: United States, Los Angeles, Antibiotics, Antimicrobial Resistance, Drug Resistance, Medicinal Chemistry, Pharmaceuticals, Therapy, Treatment. This article was prepared by Anti-Infectives Week editors from staff and other reports. Copyright 2007, Anti-Infectives Week via NewsRx.com.
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