Synthesis and evaluation of antinociceptive and anti-inflammatory effects of nitro-porphyrins

AbstractThis manuscript reports the anti-inflammatory and antinociceptive effects of 4 nitrophenyl-porphyrins: 5,10,15,20-tetra-(3-nitrophenyl)-porphyrin (TNPP), 5,10,15,20-tetra-(4-fluoro-3-nitrophenyl)-porphyrin (TpFNPP), 5,10,15,20-tetra-(4-chloro-3-nitrophenyl)-porphyrin (TpClNPP), and 5,10,15,20-tetra-(4-bromo-3-nitrophenyl)-porphyrin (TpBrNPP). The in vivo anti-inflammatory assays were tested on the acute and chronic TPA (12-O-tetradecanoylphorbol 13-acetate) induced ear edema. The in vitro anti-inflammatory assay was carried out using J774A.1 murine macrophages stimulated with LPS. All nitro-porphyrins decreased inflammation significantly in the acute model: 58.55% (TNPP), 67.49% (TpBrNPP), 67.49% (TpClNPP), and 71.32% (TpFNPP). TpFNPP (50  µM/ml) increased the production of the anti-inflammatory cytokine IL-10, and decreased the production of the pro-inflammatory cytokines IL-1β, TNF-α, and IL-6 in macrophages activated with LPS, with similar activity than indomethacin (50 µM/ml). All porphyrins showed antinociceptive activit y and lacked visible toxicity in the acute toxicity test. These results open the possibility of further studies to determine mechanisms of action, and study the influence of the structure on the activity of such compounds.
Source: Medicinal Chemistry Research - Category: Chemistry Source Type: research