Photolysis and photosensitized degradation of the diuretic drug acetazolamide

Abstract

The phototoxic diuretic drug acetazolamide ( 1) is photolabile under irradiation with UV-B (at 300 nm) light in aerobic. Also photodegradation of 1 with UV-A light (at 337 nm, N 2 laser) and photosensitizing degradation with rose bengal was observed. Two photoproducts were isolated and identified. In both the cases the same photoproducts were obtained. Sensitization reaction involving singlet oxygen lead to decomposition of acetazolamide. A photooxidation with singlet oxygen was determined as the principal photoprocess. Irradiation in presence of histidine and NaN 3 (quenches and scavenges 1O 2 ) induce a pronounced retardation of the photodecomposition rate of 1, and to the formation of a dimeric photoproduct. Also the generation of singlet oxygen was detected by trap with 2.5-dimethylfuran and furfuryl alcohol. Under argon atmosphere only this dimeric photoproduct was isolated. Acetazolamide has been shown to photosensitize the reduction of nitro blue tetrazolium in PBS, which is more efficient in deoxygenated conditions and quenched in presence of SOD. These results indicate that direct electron transfer occurs from the excited state of 1 to the substrate, and also that superoxide could be involved as an intermediate when oxygen is present. On the basis of our results, photochemical reaction mechanism of acetazolamide is postuled and discussed.