Avances en Química (Dec 2006)
Studies on the in vitro phototoxicity of the antidiabetes drug gliclazide.
Abstract
The phototoxic antidiabetes drug gliclazide (1) is photolabile under aerobic conditions and UV-B light.Irradiation of a phosphate buffered solution of 1 under oxygen atmosphere produces two photoproducts.The photochemistry of 1 involves cleavage of the S-N and C(O)-N bonds of the urea unit. Red blood celllysis photosensitized by 1 was demonstrated. Their photoproducts didn't show this effect. Inhibition ofthis process by addition of DABCO, GSH, confirmed the possibility of the participation of free radicalsin the photoinduced hemolysis. Furthermore, in a lipid-photoperoxidation test with linoleic acid the invitro phototoxicity of gliclazide was also verified. The generation of singlet oxygen during the photolysisof gliclazide was ruled out by means of the histidine and NaN3 assays. In a supplementary study theability of 1 to inhibit free radical or reactive oxygen species (.OH, 1O2, H2O2) generated in cell-freesystems was investigated using chemiluminescence and electronic absorption spectra.
