Synthesis of glutathione-/lipoic acid-porphyrin compounds as novel biocompatible antioxidants

Abstract

A novel water-soluble porphyrin derivative bearing lipoic acid and manganese complex of this compound were successfully synthesized based primarily on the amidation reaction. The desired products, P-4Lp and Mn-P-4Lp, were achieved in the overall yields of 5% and 4% respectively from commercially available starting material. All new compounds were characterized by NMR spectroscopy and mass spectrometry. Their optical properties were also investigated by UV-visible and fluorescence spectrophotometry. According to cell cytotoxicity test, IC50 of P-4Lp and Mn-P-4Lp were found in the range of 50 to 100 mg/L and more than 150 mg/L against HaCaT and HDFa cells, respectively. Thus, both products were considered to be low cytotoxicity compounds. However, based on the antioxidant activity test, no antioxidizing activity of these compounds in both kinds of cells was observed. In addition, mitochondria targeting evaluation suggested that the target porphyrin derivatives exhibited accumulation specifically in the mitochondria of the HaCaT cells.