A new approach to counteract bacteria resistance: a comparative study between moxifloxacin and a new moxifloxacin derivative in different model systems of bacterial membrane.
New drug design has been one of the major challenges to combat bacterial resistance over the past decade. Conventional antibiotics act by destroying bacterial cell wall or by blocking biosynthetic pathways necessary for its survival. Unfortunately, there has been a fast increase in multiresistance, to several conventional antibiotics, in clinical bacterial strains. Previous studies have shown that metalloantibiotics, ternary complexes of antibiotic-metal-phenanthroline, present an increased potential as antimicrobial agents. In this work moxifloxacin, a fourth-generation quinolone, with a broad spectrum of action, and its copper ternary complex (metalloantibiotic) have been study by fluorescence spectroscopy. Partition coefficients were determined and showed that while free moxifloxacin exhibits the same behaviour independently of the lipidic system tested, the metalloantibiotic presents higher partition to liposomes, in a lipid composition-dependent way. These significant differences in the interaction of the metalloantibiotic with model bacteria membranes point out for a putative change in its uptake mechanism with increased drug-lipid interaction potentiating metalloantibiotic influx.
Requimte, Faculdade de Ciências, Departamento de Química e Bioquímica, Universidade do Porto, Rua do Campo Alegre, 4169-007 Porto, Portugal.
Silvia C
SC
Lopes
Carla
C
Ribeiro
Paula
P
Gameiro
D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism; D001372:Aza Compounds / Q000737:chemistry* / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism; D024841:Fluoroquinolones; D008081:Liposomes / Q000737:chemistry; D000077266:Moxifloxacin; D011804:Quinolines / Q000737:chemistry* / Q000378:metabolism; D013050:Spectrometry, Fluorescence
D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D008081:Liposomes; D011804:Quinolines; D000077266:Moxifloxacin