Abstract:
Porphyria is a rare metabolic disease which occurs as a result of accumulation of endogenous porphyrins due to specific enzyme deficiency in the biosynthetic pathway of heme. Chloroquine is currently used in the treatment of cutaneous porphyria, although its mechanism of action is not yet well understood. It is believed that chloroquine works in porphyria by forming complexes with excess porphyrin molecules and thus enhancing their elimination from the body. Previous reports of porphyrin-chloroquine complexes have been done mostly in aqueous models. In this study, UV/Visible optical absorbance difference spectroscopy was used to study the complexation of protoporphyrin IX with chloroquine and a range of acceptor molecules in hydrophobic models. The results show that chloroquine, mefloquine, amodiaquine, quinacrine, and pyronaridine formed relatively stronger complexes compared to other molecules such as quinine, duroquinone and caffeine. Therefore, relative to chloroquine, some of the molecules with comparable or greater binding affinity to protoporphyrin IX might also be useful in the treatment of porphyria.
