Photosensitization by drugs*
Miguel A. Miranda
Departamento de Química-Instituto de Tecnología
Química UPV-CSIC, Universidad Politécnica de Valencia,
Camino de Vera s/n, E-46022-Valencia, Spain
Abstract: Certain drugs are known to elicit photosensitivity
side effects. A satisfactory understanding of the involved mechanistic
aspects is necessary to anticipate the photosensitizing potential. We
have used tiaprofenic acid (TPA), a photosensitizing nonsteroidal antiinflammatory
drug, to illustrate the methodology followed to address this problem.
After studying the photophysical and photochemical properties of TPA,
the attention has been directed towards the reactivity of its lowest
lying p-p* triplet with biomolecules. Photosensitized lipid peroxidation
occurs by a mixed type I (radicals) and type II (singlet oxygen) mechanism.
In the case of proteins, the photosensitized reactions include Tyr,
Trp, and His photodegradation, proteinprotein photocrosslinking
and drugprotein photobinding. This involves direct quenching of
the drug triplet by the amino acid residues (Tyr and Trp) or by oxygen,
followed by singlet oxygen oxidation (His and Trp). With DNA, the studies
have included comet assay, induction of single-strand breaks in supercoiled
DNA, and reaction with 2'-deoxyguanosine and thymidine. Product studies,
together with time-resolved measurements, have shown that the fastest
reaction occurs with purine bases, by a mechanism involving both radical
and singlet oxygen processes. The employed methodology can be of general
use to investigate the mechanistic aspects of photosensitization by
drugs.
*Lecture presented at the XVIIIth IUPAC Symposium on
Photochemistry, Dresden, German , 22-27 July 2000.Other presentations
are published in this issue, pp.395-548.
