Journal of Chromatography A, 655 (1993) 177-184 Elsevier Science Publishers B.V., Amsterdam CHROM. 25 109 Influence of the chromatographic capacity factor (log k’) as an index of lipophilicity in the antibacterial activity of a series of 6fluoroquinolones Relationship between physico-chemical and structural properties and their hydrophobicity* zyxwvutsrqponmlkjihgfedcbaZYXWVUTS C. Martorell* Research Department of ITEVE, S.A. Laboratories, Passeig Prim, 32 6a pt., Reus, 43202 Tarragona (Spain) A.C. Calpena and E. Escribano Pharmacokinetics and Biopharmaceutics Laboratory, School of Pharmacy, University of Barcelona, Barcelona (Spain) J.M . Poblet School of Chemistry, University of Tarragona, Tarragona (Spain) J. Freixas Research Department of ITEVE, S.A. Laboratories, Passeig Prim, 32 6a Pt., Reus, 43202 Tarragona (Spain) (First received December IOth, 1992; revised manuscript received March 17th, 1993) ABSTRACT The aim of this study was to establish the influence of lipophilicity on the antibacterial activity (log l/MIC,,) of 22 fluoroquinolones and to assess the influence of their electronic, steric and topological properties on their hydrophobic&y. The lipophilicity of the compounds, expressed as the chromatographic capacity factor (log k’), was determined by ion-pair reversed-phase HPLC. On the basis of the mathematical models developed, an attempt was made to confirm the mechanism of interaction of the quinolones with DNA-gyrase proposed previously. INTRODUCTION Fluoroquinolones are a family of antibacterial agents extensively used in both human and veterinary clinics. They are bactericides and act by inhibiting bacterial DNA-gyrase [l]. In 1962, Lesher et al. [2] isolated nalidixic acid (Fig. 1) as a by-product in the synthesis of chloroauine. and 2 vears later it was introduced L , , * Corresponding author. into general practice for the treatment of urinary *Presented at the 21st Scientific Meeting of the Spanish infections [3]. Later, structural modifications Group of Chromatography and Related Techniques, were made to the basic skeleton of nalidixic acid Granada, October 21-23, 1992. and new derivatives were synthesized, e.g., ox- 0021-9673/93/$06.00 @ 1993 Elsevier Science Publishers B.V. All rights reserved