Design, synthesis, and antibacterial activities of neomycin-lipid conjugates: polycationic lipids with potent gram-positive activity.
Aminoglycoside antibiotics and cationic detergents constitute two classes of clinically important drugs and antiseptics. Their bacteriological and clinical efficacy, however, has decreased recently due to antibiotic resistance. We have synthesized aminoglycoside-lipid conjugates in which the aminoglycoside neomycin forms the cationic headgroup of a polycationic detergent. Our results show that neomycin-C16 and neomycin-C20 conjugates exhibit strong Gram-positive activity but reduced Gram-negative activity. The MIC of neomycin-C16 (C20) conjugates against methicillin-resistant Staphylococcus aureus (MRSA) is comparable to clinically used antiseptics.
Bera
Smritilekha
S
Department of Chemistry, University of Manitoba, Winnipeg, Manitoba, Canada.
Zhanel
George G
GG
Schweizer
Frank
F
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000254:growth & development; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000254:growth & development; D057927:Hydrophobic and Hydrophilic Interactions; D008055:Lipids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009355:Neomycin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011073:Polyamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000071228:Polyelectrolytes; D013237:Stereoisomerism
D000900:Anti-Bacterial Agents; D008055:Lipids; D009355:Neomycin; D011073:Polyamines; D000071228:Polyelectrolytes