Photosensitizing activity of thiocolchicoside: photochemical and in vitro phototoxicity studies

The phototoxic drug thiocolchicoside (2-dimethoxy-2-glucosidoxythiocolchicine, 1), is photolabile under irradiation with UV-A light from TL 100 W-P Philips bulbs (at lambda max 355 nm) light and also with a N2 laser (at 337 nm) in aerobic and anaerobic conditions. Irradiation of a methanol solution of 1 produces two photoproducts without a glucoside group. One of these lost the methylthio-group, while the other is oxidized (only under aerobic conditions) to sulfoxide. The formation of singlet oxygen by photolysis of 1 was evidenced by trapping with 2,5-dimethylfuran (GC-MS), furfuryl alcohol, 1,3-cyclohexadiene-1,4-diethanoate (HPLC) and by the histidine test as 1O2 scavengers. Thiocolchicoside has been shown to photosensitize the reduction of nitro blue tetrazolium by direct electron transfer mechanism, when irradiated under the same conditions as for photolysis. Oxygen may also be involved in this electron transfer reaction to form the superoxide anion radical. Thiocolchicoside was screened in vitro in different concentrations for UV-Vis-induced phototoxic effects in a photohemolysis test, in the presence and absence of different radical scavengers, singlet oxygen and superoxide radical quenchers. In addition, 1 photosensitized the peroxidation of linoleic acid, monitored by the UV-detection of dienic hydroperoxides. Studies on peripheral blood mononuclear cells (lymphocytes) demonstrated phototoxic effects on them. Protection by GSH, DABCO, sodium azide and SOD are indicative of both Type I and II photosensitization pathways mediated by free radicals and singlet molecular oxygen.