Synthesis, anti-inflammatory activity and modeling studies of cycloartane-type terpenes derivatives isolated from Parthenium argentatum.

Abstract

The 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced edema model in mice determined the anti-inflammatory activities in vivo of argentatins A, B and D, the main cycloartenol-type triterpenes present in Parthenium argentatum. Our results showed that argentatin B (ED50=1.5×10(-4)mmol/ear) and argentatin A (ED50=2.8×10(-4)mmol/ear) were more potent anti-inflammatory agents than indomethacin (ED50=4.5×10(-4)mmol/ear), the reference drug. Based on these findings, we decided to evaluate 13 derivatives of argentatins A and B. All the derivatives showed anti-inflammatory activity in the TPA-induced edema model in mice. The most active compound was 25-nor-cycloart-3, 16-dione-17-en-24-oic acid, obtained from argentatin A (ED50=1.4×10(-4)mmol/ear). Argentatin B was assayed as inhibitor of COX-2 activity one of the key enzymes involved in the TPA assay. The results showed that argentatin B at 15μM doses inhibited 77% COX-2 activity. Docking studies suggest that argentatin B interacts with Arg 120, a key residue for COX-2 activity.

• Authors: Juan Carlos Romero, Adriana Martínez-Vázquez, Maribel Pineda Herrera, Karina Martinez-Mayorga, Hortensia Parra-Delgado, Francisco J Pérez-Flores, Mariano Martínez-Vázquez
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 22 Issue 24 Pg. 6893-8 (Dec 15 2014) ISSN: 1464-3391 [Electronic] England
• PMID: 25456078 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Cyclooxygenase 2 Inhibitors
• Terpenes
• Triterpenes
• argentatin B
• argentatin A
• Nitric Oxide
• cycloartane
• Cyclooxygenase 2
• Tetradecanoylphorbol Acetate

Topics

• Animals
• Anti-Inflammatory Agents (chemical synthesis, pharmacology, therapeutic use)
• Asteraceae (chemistry, metabolism)
• Binding Sites
• Cell Line
• Cell Survival (drug effects)
• Cyclooxygenase 2 (chemistry, metabolism)
• Cyclooxygenase 2 Inhibitors (chemistry, metabolism)
• Edema (chemically induced, drug therapy)
• Macrophages (cytology, drug effects, metabolism)
• Male
• Mice
• Molecular Docking Simulation
• Nitric Oxide (metabolism)
• Protein Structure, Tertiary
• Terpenes (chemistry, isolation & purification, therapeutic use)
• Tetradecanoylphorbol Acetate (toxicity)
• Triterpenes (chemistry, isolation & purification, therapeutic use)