Photosensitizing properties of Actarit, an antirheumatic drug.
The photobiological properties of 4-acetylaminophenylacetic acid (Actarit, ACT, MS-932, CAS 18699-02-0) were studied using in vitro phototoxicity assays: photohemolysis, photoperoxidation of linoleic acid and Candida sp phototoxicity test. ACT reduced nitro blue tetrazolium (NBT) when irradiated with lambda > or = 300 nm in deoxygenated aqueous buffer solution (pH 7.4). The photohemolysis rate and photoperoxidation of linoleic acid were inhibited significantly by reduced glutathione. ACT was phototoxic to Candida sp. The isolation and identification of the photodegradation products of ACT in phosphate buffered saline solution (pH 7.4) and methanol were studied under aerobic conditions. Four compounds were identified and two of them isolated and characterized by spectroscopic methods. A photodecarboxylation with the participation of oxygen via a type I mechanism was proposed for the photodegradation of ACT which undergoes direct electron transfer from the excited state of ACT carboxylate and homolytic rupture of the alpha-carbon bond. A photodynamic mechanism involving radicals and electron transfer reactions was suggested for the observed in vitro phototoxicity.
Laboratorio de Fotoquímica y Fotobiología, Departamento de Química, Universidad Simón Bolivar, Caracas, Venezuela. ncanudas@usb.ve
Nieves
N
Canudas
Lillian
L
Figueroa
Delimar
D
Zamora
José E
JE
Villamizar
Arlen
A
Guedez
Juan M
JM
Fuentes
Cristina
C
Castelli
Antonieta
A
Taddei
D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000737:chemistry; D002175:Candida / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects / Q000528:radiation effects; D005609:Free Radicals / Q000737:chemistry; D006461:Hemolysis / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008027:Light; D019787:Linoleic Acid / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D010545:Peroxides / Q000737:chemistry; D010648:Phenylacetates / Q000009:adverse effects* / Q000737:chemistry; D010777:Photochemistry; D017319:Photosensitizing Agents; D013056:Spectrophotometry, Ultraviolet
D018501:Antirheumatic Agents; D005609:Free Radicals; D007202:Indicators and Reagents; D010545:Peroxides; D010648:Phenylacetates; D017319:Photosensitizing Agents; C052562:4-(acetylamino)benzeneacetic acid; D019787:Linoleic Acid