Understanding of the Photoallergic Properties of Fluoroquinolones: Photoreactivity of Lomefloxacin with Amino Acids and Albumin

Abstract

Although the phototoxic and photoallergic properties of fluoroquinolone antibiotics (FQ) are remarkable, the mechanisms involved in these processes are not completely understood. For this reason, it is considered worthwhile to study in detail the photochemical interactions of lomefloxacin (LFX) and its N-acetyl derivative ALFX, two 6,8-dihalogenated fluoroquinolones, with the most abundant protein in human plasma (human serum albumin, HSA) to analyze their covalent binding. Fluorescence measurements and laser flash photolysis experiments performed in this work have revealed that N-acetylation of the LFX piperazinyl moiety produces an important increase of the drug affinity to albumin. Thus, while the association constant (Ka) for the LFX···HSA complex is below 10(3) M(-1), the Ka for the HSA···ALFX complex resulted in ca. 5 × 10(3) M(-1). Interestingly, LFX is mainly located at site I of HSA, while ALFX shows no preference for site I or II. A high reactivity between the aryl cations generated from (A)LFX dehalogenation and Trp and Tyr together with the generation of covalent adducts between the FQ and these amino acids was observed. However, the interactions between the FQ singlet excited state and albumin in FQ···HSA complexes seem to be the key process of FQ covalent binding to albumin. Moreover, our findings have shown a correlation between the photobinding properties of dihalogenated fluoroquinolones to HSA and their FQ···HSA association constants.