In vitro cytotoxicity study of oxaziridines generated after chlordiazepoxide, demoxepam, and desmethylchlordiazepoxide UV irradiation.
The cytotoxicity of oxaziridines photogenerated after irradiation of chlordiazepoxide (CDZ) and its metabolites was investigated in vitro by a MTT assay on P388 leukemia and B16 melanoma cell lines and compared with that of the anticancer drug, melphalan. For the longer time-exposure experiment, oxaziridines had the same cytotoxicity as melphalan and this toxicity was higher when oxaziridines were photogenerated in the presence of cells. In conclusion, oxaziridines generated after CDZ, demoxepam, and desmethylchlordiazepoxide ultraviolet irradiation exhibited cytotoxicity activity against cancer cell lines. A possibility of CDZ use within the context of photodynamic therapy as a treatment for small, superficial tumors should not be excluded, because oxaziridines can be generated locally by skin-tumor local irradiation after CDZ topical administration.
Laboratory of Toxicology, Bioanalytical Chemistry, and Applied Physical Chemistry, Institute of Pharmacy, Free University of Brussels, Brussels, Belgium. mustapha_ouedraogo@yahoo.fr
Moustapha
M
Ouédraogo
Eve
E
De Maesschalck
Valérie
V
Soentjens-Werts
Jacques
J
Dubois
D000818:Animals; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D001388:Aziridines / Q000633:toxicity; D001569:Benzodiazepines / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects; D002707:Chlordiazepoxide / Q000494:pharmacology / Q000627:therapeutic use; D004354:Drug Screening Assays, Antitumor; D007941:Leukemia P388 / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D008546:Melanoma, Experimental; D008558:Melphalan / Q000009:adverse effects; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011827:Radiation; D014466:Ultraviolet Rays
C033132:aziridine; D001388:Aziridines; D001569:Benzodiazepines; D002707:Chlordiazepoxide; C000869:demoxepam; D008558:Melphalan