Topical Anti-inflammatory Activity of New Hybrid Molecules of Terpenes and Synthetic Drugs.

Abstract

The aim of the study was to assess changes in the activity of anti-inflammatory terpenes from Chilean medicinal plants after the formation of derivatives incorporating synthetic anti-inflammatory agents. Ten new hybrid molecules were synthesized combining terpenes (ferruginol (1), imbricatolic acid (2) and oleanolic acid (3)) with ibuprofen (4) or naproxen (5). The topical anti-inflammatory activity of the compounds was assessed in mice by the arachidonic acid (AA) and 12-O-tetradecanoyl phorbol 13-acetate (TPA) induced ear edema assays. Basal cytotoxicity was determined towards human lung fibroblasts, gastric epithelial cells and hepatocytes. At 1.4 µmol/mouse, a strong anti-inflammatory effect in the TPA assay was observed for oleanoyl ibuprofenate 12 (79.9%) and oleanoyl ibuprofenate methyl ester 15 (80.0%). In the AA assay, the best activity was observed for 12 at 3.2 µmol/mouse, with 56.8% reduction of inflammation, in the same range as nimesulide (48.9%). All the terpenyl-synthetic anti-inflammatory hybrids showed better effects in the TPA assay, with best activity for 6, 12 and 15. The cytotoxicity of the compounds 8 and 10 with a free COOH, was higher than that of 2. The derivatives from 3 were less toxic than the triterpene. Several of the new compounds presented better anti-inflammatory effect and lower cytotoxicity than the parent terpenes.

• Authors: Cristina Theoduloz, Carla Delporte, Gabriela Valenzuela-Barra, Ximena Silva, Solange Cádiz, Fernanda Bustamante, Mariano Walter Pertino, Guillermo Schmeda-Hirschmann
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 20 Issue 6 Pg. 11219-35 (Jun 18 2015) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 26096431 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Terpenes

Topics

• Administration, Topical
• Animals
• Anti-Inflammatory Agents (chemical synthesis, chemistry, pharmacology)
• Cell Line
• Disease Models, Animal
• Edema (chemically induced, drug therapy)
• Humans
• Mice
• Terpenes (chemical synthesis, chemistry, pharmacology)