Drug- photosensitised modifications of proteins

Several topical or systemic drugs may result in some photosensitivity reactions under light exposure. Wavelengths within the UV-A (320-400 nm) range are more likely to cause drug-induced photosensitization, although occasionally UV-B (290-320 nm) can also be responsible for such effects. Proteins are one of the main biological targets of this damage. The mechanisms involved in chemical changes of amino acids and proteins upon irradiation are mediated by radicals (Type I), drug-derived peroxides, singlet oxygen (Type II) and direct binding (Type III), giving rise to drug-protein photoadducts with nucleophilic aminoacids (e.g., serine, tyrosine, lysine), protein photocross-linking (drug-protein or protein-protein), photodegradation or photooxidation of aminoacids (e.g., tryptophan, tyrosine, cysteine/cystine, phenilalanine). The photosensitised modification of proteins and enzymes could lead to loss of their biological functions with damage to some organs and the occurrence of phototoxic side effects as well as to photoallergic reactions when the immune system is involved in the skin. Phenothiazines (fluphenazine, chlorpromazine, promethazine), non selective NSAIDs (tiaprophenic acid) and Coxibs (celecoxib), Diuretics (hydrochlorothiazide), 5-fluorouracil, Corticosteroids (fluocinolone, flumethasone), chlorochresol, are examples of pharmaceutical compounds able to induce protein modifications under UV irradiation. References: H. Alenius, D. W. Roberts, Y.Tokura, A. Lauerma, G. Patlewicz and M. S. Roberts, Skin, drug and chemical reactions Drug Discovery Today: Disease Mechanisms, Vol. 5, No.2, e211-e220 (2008) Miranda M.A. J.V. Castell, D. Hernandez et al., Drug-Photosensitized Protein Modification: Identification of the Reactive Sites and Elucidation Of Reaction Mechanisms with Tiaprofenic Acid/Albumin as Model System Chem.Res. Toxicol., 11, 172-177 (1998) Miranda M.A. J.V. Castell, D. Hernandez et al., Mechanisms of Photosensitizion by Drugs: Involvement of Tyrosines in the Photomodification of Proteins Mediated by Tiaprofenic Acid In Vitro, Toxicol. In Vitro, 11 , 653-659 (1997) Caffieri S., Miolo G., Seraglia S., Dalzoppo D., Toma F.M., van Henegouwen G.M., Photoaddition of fluphenazine to nucleophiles in peptides and proteins. Possible cause of immune system side effects, Chem. Res. Toxicol., 20, 1470-6 (2007