NO-donor phenols: a new class of products endowed with antioxidant and vasodilator properties

Donatella Boschi; Gian Cesare Tron; Loretta Lazzarato; Konstantin Chegaev; Clara Cena; Antonella Di Stilo; Marta Giorgis; Massimo Bertinaria; Roberta Fruttero; Alberto Gasco

doi:10.1021/jm0510530

NO-donor phenols: a new class of products endowed with antioxidant and vasodilator properties

J Med Chem. 2006 May 18;49(10):2886-97. doi: 10.1021/jm0510530.

Authors

Donatella Boschi¹, Gian Cesare Tron, Loretta Lazzarato, Konstantin Chegaev, Clara Cena, Antonella Di Stilo, Marta Giorgis, Massimo Bertinaria, Roberta Fruttero, Alberto Gasco

Affiliation

¹ Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, Via Pietro Giuria 9, 10125 Torino, Italy.

PMID: 16686532
DOI: 10.1021/jm0510530

Abstract

The synthesis and study of the antioxidant and vasodilator properties of a new class of phenols able to release nitric oxide are described. The products were designed through a symbiotic approach using selected phenols and selected nitrooxy and furoxan NO-donors as reference models. The antioxidant activities of the hybrid products were assessed by detecting the 2-thiobarbituric acid reactive substances (TBARS) produced in the ferrous salt/ascorbate-induced autoxidation of lipids present in microsomial membranes of rat hepatocytes. The vasodilator activity was assessed on rat aortic strips precontracted with phenylephrine. Some of the products (13, 35, 37, 60-62, 64) behave principally as vasodilators and others as antioxidants (24, 32, 72), and the two properties are relatively balanced in 19, 41, and 68. Further in vivo studies should clarify whether some of these products may become preclinical candidates for the treatment of cardiovascular disease underpinned by atheroma.

Publication types

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

MeSH terms

Animals
Antioxidants / chemical synthesis*
Antioxidants / chemistry
Antioxidants / pharmacology
Aorta, Thoracic / drug effects
Aorta, Thoracic / physiology
In Vitro Techniques
Lipid Metabolism / drug effects
Male
Microsomes, Liver / drug effects
Microsomes, Liver / metabolism
Muscle Contraction / drug effects
Muscle, Smooth, Vascular / drug effects
Muscle, Smooth, Vascular / physiology
Nitrates / chemistry
Nitric Oxide Donors / chemical synthesis*
Nitric Oxide Donors / chemistry
Nitric Oxide Donors / pharmacology
Oxadiazoles / chemistry
Oxidation-Reduction
Phenols / chemical synthesis*
Phenols / chemistry
Phenols / pharmacology
Rats
Rats, Wistar
Structure-Activity Relationship
Thiobarbituric Acid Reactive Substances / metabolism
Vasodilator Agents / chemical synthesis*
Vasodilator Agents / chemistry
Vasodilator Agents / pharmacology

Substances

Antioxidants
Nitrates
Nitric Oxide Donors
Oxadiazoles
Phenols
Thiobarbituric Acid Reactive Substances
Vasodilator Agents
furoxans