UV radiation protecting efficacy of cysteine derivatives, studies with UVA-induced binding of 8-MOP and CPZ to rat epidermal biomacromolecules in vivo.
With the aim of optimizing the UV radiation protecting efficacy of N-acetylcysteine (NAC), the following topically applied cysteine derivatives were investigated: N-acetylcysteine ethylester (NACET), S-acetylcysteine ethylester (SACET), cysteine ethylester (CYSET), N,S-diacetylcysteinamide (SNACA), N,S-diacetylcysteine (SNAC) and N,S-diacetylcysteine ethylester (SNACET). As a measure for protection the inhibition of in vivo irreversible photobinding of the labelled phototoxic drugs chlorpromazine (CPZ) and 8-methoxypsoralen (8-MOP) to rat epidermal biomacromolecules was used. The duration of protection of the cysteine derivatives was shortened by S-acetylation, N-acetylation and carboxyl derivatization. Compounds with a free thiol group showed a long-lasting presence in the stratum corneum, probably by the formation of mixed disulphides with proteins. The intrinsic protecting efficacy with respect to the total epidermis increased in the order CYSET < SNACET,SNACA,SACET < NACET, SNAC,NAC. The results of this study are discussed in view of susceptibility to oxidation, epidermal bioavailability and metabolic activation. With respect to the viable epidermis we postulate that NACET and SNAC have the most promising properties as UV protective agents.
Van den Broeke
L T
LT
Department of Medicinal Photochemistry, Leiden/Amsterdam Center for Drug Research, Leiden University, The Netherlands.
Beijersbergen van Henegouwen
G M
GM
D000287:Administration, Topical; D000818:Animals; D001682:Biological Availability; D002746:Chlorpromazine / Q000378:metabolism*; D003545:Cysteine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology*; D004563:Electrochemistry; D005260:Female; D046911:Macromolecular Substances; D008730:Methoxsalen / Q000378:metabolism*; D010084:Oxidation-Reduction; D011837:Radiation-Protective Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects*; D013997:Time Factors; D014466:Ultraviolet Rays
D046911:Macromolecular Substances; D011837:Radiation-Protective Agents; D003545:Cysteine; D002746:Chlorpromazine; D008730:Methoxsalen