Determination of the partition coefficients of a homologous series of ciprofloxacin: influence of the N-4 piperazinyl alkylation on the antimicrobialactivity

Partitioning of a fluoroquinolone antibiotic, ciprofloxacin, and its N-pipe razinyl alkyl derivatives, between octanol or Escherichia toll lipid membra ne extract and aqueous buffer pH 7.4, was studied. The experimental partiti on coefficients (P-exp) were corrected at this pH using an expression that includes the microconstant values of each compound. The relationship betwee n the corrected partition coefficients expressed as log P (thermodynamic pa rtition coefficient) and the diffusion through the lipid bilayers ('hydroph obic pathway') of entry has been considered here. In this work, we have exp lored the possibility of using our model to provide physicochemical evidenc es to support such a via. The correlation between log P values and antibact erial activities (expressed as minimal inhibitory concentration (MIC) value s) of the homologous series of antibiotics against different bacteria were studied. A parabolic behaviour was observed which evidenced that the only i ncrease in lipophilicity does not result in an enhanced antimicrobial activ ity for the homologous family studied. (C) 2001 Elsevier Science B.V. All r ights reserved.