Photoinduced modifications by fluoroquinolone drugs in bovine serum albumin (BSA) and ribonuclease A (RNAse) as model proteins

Photosensitized protein oxidation by drugs, with the consequent modification of their structure is thought to be responsible for the occurrence of phototoxic phenomena such as photoallergy and loss of biological functions. In this paper we have investigated in detail the interaction of four fluoroquinolones namely ciprofloxacin, lomefloxacin, norfloxacin and ofloxacin with two proteins such as Bovine Serum Albumin (BSA) and Ribonuclease A (RNAse A) chosen as models. The interactions between the four drugs and the proteins, were studied by absorption and emission spectroscopy. Photophysical experiments were carried out in aqueous solutions by stationary and time-resolved fluorimetry and by laser flash photolysis, in the absence and in the presence of the proteins to obtain information on the various decay pathways of the excited states of the drugs and on transient species formed upon irradiation. In parallel we have investigated by a series of biochemical assays the photoinduced modifications exerted by the four drugs. The obtained results showed that the four drugs are able to photooxidize proteins with the formation of protein-protein cross-link. This effect was also confirmed in isolated erythrocyte membranes. Furthermore the effect of the fluoroquinolones was also evaluated on isolated aromatic aminoacids. In this context the four drugs are able to photodamage in particular tyrosine and histidine. These results are important in the light of the growing interest for the comprehension of the mechanism of phototoxicity induced by these antibacterial drugs.