RESUMO
Novel glyoxylate- and glyoxamide-derived metalloporphyrins 26-58 were synthesized and evaluated as potential superoxide dismutase (SOD) mimetics. Relative to previously studied MnTBAP analogues, the glyoxylate-derived metalloporphyrins 32, 39, and 54 and glyoxamide-derived metalloporphyrin 49, exhibited enhanced activity in the SOD assay and the majority of the analogues in the current series showed enhanced inhibition of lipid peroxidation and catalase activity.
Assuntos
Antioxidantes/síntese química , Metaloporfirinas/síntese química , Mimetismo Molecular , Superóxido Dismutase/química , Antioxidantes/farmacologia , Catalase/antagonistas & inibidores , Glioxilatos/química , Peroxidação de Lipídeos/efeitos dos fármacos , Metaloporfirinas/química , Metaloporfirinas/farmacologia , Relação Estrutura-Atividade , Compostos de Sulfonilureia/química , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
Carboxylic ester and amide-substituted analogues of [5,10,15,20-tetrakis(4-carboxyphenyl)-porphyrinato]manganese(III) chloride (MnTBAP) were synthesized and assayed as potential superoxide dismutase (SOD) mimetics. The tetraester analogues 4a and 4b were found to have comparable SOD activity to the known SOD mimetic MnTBAP, while amides 4c-4e exhibited reduced SOD activity. In the substituted methyl benzoate/acid and disubstituted porphyrin series, analogues 12c, 12f, and 12m were found to have comparable to improved SOD activity relative to MnTBAP and analogues 12j, 13a, and 13d exhibited improved activity in both the SOD and thiobarbituric acid reactive species (TBARS) assays relative to MnTBAP.
