Drug-biomolecule interactions in the excited states

Abstract

Drug-biomolecule interactions in the excited state are relevant from a photobiological point of view as they can be correlated with a number of photosensitization disorders such as photocarcinogenicity, photoallergy, phototoxicity, etc. Nonsteroidal antiinflammatory 2-arylpropionic acids and antibacterial fluoroquinolones have been selected as typical examples of photoactive drugs. Protein photosensitization has revealed photoadduct formation; the major amino acids involved are Tyr, Trp, and His. Generation of specific antibodies has allowed us to identify relevant structures of the drug epitopes. Then, drugs have been submitted to systematic steady-state and time-resolved studies on their photophysical properties, alone and in the presence of biomolecules: proteins, DNA, and their simple building blocks. The results are discussed in the framework of the chemical mechanisms underlying photosensitization by drugs and also in connection with the potential of drug excited states as (chiral) reporters for the binding sites of biomolecules.

Water concentration dependent photochemistry of ketoprofen in aqueous solutions

“…1,2 A large number of studies have been performed in recent years on both the phototoxic and photoallergic reactions induced by KP so as to estimate the safety of KP and also to investigate the mechanism(s) of the photosensitivity reactions when KP is exposed to UV light. 3,4 These results show that the photochemistry of KP in aqueous solution is strongly influenced by its acid-base chemistry. 5 The neutral form of ketoprofen that exists in the absence of a base exhibits typical benzophenone-like photochemistry, 5,6 while the deprotonated ketoprofen that exists in the presence of a base undergoes an efficient photodecarboxylation process.…”

Supramolecular photochemistry of drugs in biomolecular environments

“…SUP and KP induce analogous modifications in the SA matrix. 5 Tyr has been indicated to be involved in the formation of photoadducts. Full structural characterization of the adducts has not been achieved, but the use of highly specific antibodies to drug chemical epitopes has allowed discrimination between the different modes by which TPA, SUP and KP photobind to BSA, evidencing that the binding geometry critically depends on the drug molecular structure.…”

“…During the last decades a lot of basic research has focused on the photochemistry of drugs in homogeneous solution and in systems mimicking a biological environment. [1][2][3][4][5] This research was driven by the need to understand and control drug-induced phototoxicity and photoallergy during treatment, 6 but also inspired scientists looking for innovative photochemotherapies. Indeed therapeutic approaches based on drugs activatable by light attracted interest and developed more and more gaining a marginal, but significant role in clinical practice.…”

Photoinduced electron transfer photodegradation of photosensitive diuretic drug-xipamide

“…Many photosensitization reactions may be explained on the basis of the mechanism Type I (radical mediated) or Type II (singlet oxygen mediated). There are photosensitizing drugs of varied structural variety and significant variations in the phototoxic mechanisms must be expected depending on the difference in structural features [4]. It is therefore highly significant to study photochemical reaction of each individual phototoxic drug.…”