Thiols as potential UV radiation protectors: an in vitro study.
The following thiols were investigated with regard to their possible UV-radiation protective properties: captopril, cysteamine, ergothioneine, mesna, mercaptopropionylglycine, N-acetylcysteine, and penicillamine. As a measure for protection, the inhibition of in vitro irreversible photobinding of the labeled phototoxic drugs chlorpromazine (CPZ) and 8-methoxypsoralen (8-MOP) to protein and DNA was used. Besides photobinding to biomacromolecules, the photodegradation of CPZ and the formation of promazine (PZH) and hydroxypromazine (PZOH) were measured as well. Because of the H-atom and electron donating capacity of the thiols, the ratio [PZOH]/[PZH] was expected to be decreased and the photodegradation of CPZ was expected to be higher in the presence of thiols. Maximum inhibition of CPZ photobinding ranged for the different thiols between 21-100% (DNA) and 17-87% (human serum albumin). All thiols enhanced the photodegradation of CPZ (19-84%) and inhibited the ratio [PZOH]/[PZH] (90-97%). 8-MOP photobinding to human serum albumin was also clearly inhibited (75-96%), but remarkably less to DNA (2-41%). This study indicates that thiols are able to cope with a variety of reactive species. Scavenging of radicals, quenching of singlet molecular oxygen species and reaction with excited states seem to be essential mechanisms involved with this process.
Department of Medicinal Chemistry, Leiden University, Netherlands.
L T
LT
van den Broeke
G M
GM
Beyersbergen van Henegouwen
D002746:Chlorpromazine / Q000737:chemistry / Q000378:metabolism* / Q000528:radiation effects; D004247:DNA / Q000378:metabolism*; D006801:Humans; D008730:Methoxsalen / Q000378:metabolism*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D012709:Serum Albumin / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D014466:Ultraviolet Rays
D011837:Radiation-Protective Agents; D012709:Serum Albumin; D013438:Sulfhydryl Compounds; D004247:DNA; D002746:Chlorpromazine; D008730:Methoxsalen