Anti-inflammatory and antioxidant properties of a novel resveratrol-salicylate hybrid analog

Fahad S Aldawsari; Rafael Pazinatto Aguiar; Luiz Alexandre Marques Wiirzler; Rodrigo Aguayo-Ortiz; Naif Aljuhani; Roberto Kenji Nakamura Cuman; José L Medina-Franco; Arno G Siraki; Carlos A Velázquez-Martínez

doi:10.1016/j.bmcl.2016.01.069

Anti-inflammatory and antioxidant properties of a novel resveratrol-salicylate hybrid analog

Bioorg Med Chem Lett. 2016 Mar 1;26(5):1411-5. doi: 10.1016/j.bmcl.2016.01.069. Epub 2016 Jan 25.

Authors

Fahad S Aldawsari¹, Rafael Pazinatto Aguiar², Luiz Alexandre Marques Wiirzler², Rodrigo Aguayo-Ortiz³, Naif Aljuhani⁴, Roberto Kenji Nakamura Cuman², José L Medina-Franco³, Arno G Siraki⁵, Carlos A Velázquez-Martínez⁵

Affiliations

¹ Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2E1, Canada. Electronic address: aldawsar@ualberta.ca.
² Department of Pharmacology and Therapeutics, State University of Maringá, Maringá, PR 870020-900, Brazil.
³ Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, México City, DF 04510, Mexico.
⁴ Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2E1, Canada; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Taibah University, Madinah, Saudi Arabia.
⁵ Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2E1, Canada.

PMID: 26850006
DOI: 10.1016/j.bmcl.2016.01.069

Abstract

Resveratrol is a natural compound with a plethora of activities as well as limitations. We recently reported a series of resveratrol-salicylate analogs with potential chemopreventive activity. Herein, we report the anti-inflammatory and antioxidant properties of these resveratrol derivatives. Using an in vitro COX inhibition assay, and two in vivo protocols (carrageenan-induced peritonitis and paw edema), we identified a novel compound (C10) as a potent anti-inflammatory agent. The enhanced potency of C10 was associated with the ability of C10 to decrease the activity of myeloperoxidase (MPO) enzyme at 10mg/kg, whereas resveratrol and it's natural analog (TMS) did not exert the same effect. Additionally, C10 significantly reduced the concentration of intracellular reactive oxygen species. Because of the proven association between cancer, inflammation, and oxidative stress, we believe that C10 is a promising chemopreventive molecule.

Keywords: Chemoprevention; Inflammation; Myeloperoxidase; Resveratrol; Salicylate.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Administration, Oral
Animals
Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
Anti-Inflammatory Agents, Non-Steroidal / chemistry
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
Antioxidants / chemical synthesis
Antioxidants / chemistry
Antioxidants / pharmacology*
Carrageenan
Cyclooxygenase Inhibitors / chemical synthesis
Cyclooxygenase Inhibitors / chemistry
Cyclooxygenase Inhibitors / pharmacology
Dose-Response Relationship, Drug
Edema / drug therapy*
Hep G2 Cells
Humans
Hydrogen Peroxide / antagonists & inhibitors
Hydrogen Peroxide / pharmacology
Mice
Molecular Structure
Oxidative Stress / drug effects
Peritonitis / drug therapy*
Prostaglandin-Endoperoxide Synthases / metabolism
Reactive Oxygen Species / metabolism
Resveratrol
Salicylates / chemistry
Salicylates / pharmacology*
Stilbenes / administration & dosage
Stilbenes / chemistry
Stilbenes / pharmacology*
Structure-Activity Relationship

Substances

Anti-Inflammatory Agents, Non-Steroidal
Antioxidants
Cyclooxygenase Inhibitors
Reactive Oxygen Species
Salicylates
Stilbenes
Carrageenan
Hydrogen Peroxide
Prostaglandin-Endoperoxide Synthases
Resveratrol