Determination of the partition coefficients of a homologous series of ciprofloxacin: influence of the N-4 piperazinyl alkylation on the antimicrobial activity.
Partitioning of a fluoroquinolone antibiotic, ciprofloxacin, and its N-piperazinyl alkyl derivatives, between octanol or Escherichia coli lipid membrane extract and aqueous buffer pH 7.4, was studied. The experimental partition coefficients (Pexp) were corrected at this pH using an expression that includes the microconstant values of each compound. The relationship between the corrected partition coefficients expressed as logP (thermodynamic partition coefficient) and the diffusion through the lipid bilayers ('hydrophobic pathway') of entry has been considered here. In this work, we have explored the possibility of using our model to provide physicochemical evidences to support such a via. The correlation between logP values and antibacterial activities (expressed as minimal inhibitory concentration (MIC) values) of the homologous series of antibiotics against different bacteria were studied. A parabolic behaviour was observed which evidenced that the only increase in lipophilicity does not result in an enhanced antimicrobial activity for the homologous family studied.
Vázquez
J L
JL
Laboratori V. Departament de Fisicoquímica, Facultat de Farmácia, Universitat de Barcelona, E-08028, Barcelona, Spain.
Merino
S
S
Domenech
O
O
Berlanga
M
M
Viñas
M
M
Montero
M T
MT
Hernández-Borrell
J
J
D000478:Alkylation; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000031:analogs & derivatives / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D016014:Linear Models; D008826:Microbial Sensitivity Tests; D010879:Piperazines / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000890:Anti-Infective Agents; D010879:Piperazines; D002939:Ciprofloxacin