RESUMEN
Oxidants play a significant role in the pathogenesis of a number of disorders such as inflammation, rheumatoid arthritis, asthma, psoriasis and contact dermatitis leading to oxidative stress. Oxidative stress may be defined as an imbalance between cellular production of reactive oxygen species (ROS) and antioxidant defense mechanisms. ROS (e.g., superoxide radical, peroxynitryl, hydroxyl radical and hydrogen peroxide) are constantly produced as a result of metabolic reactions in living systems. The aim of this review is to describe recent developments in the study of antioxidants and their role in preventing the formation of ROS. The processes associated with inflammatory responses are complex and often involve ROS. There are many mediators, which initiate and amplify the inflammatory response such as histamine, serotonin, pro-inflammatory cytokines (interleukin-1B (IL-1b) and tumor necrosis factor (TNF-alpha), inflammatory cells (leukotrienes, macrophages), metabolic products of arachidonic acid (thomboxane A(2), prostaglandins and leukotrienes). The first part of this review focuses on the role of ROS in inflammation. The second part concerns synthetic antioxidants with antiinflammatory activity, and the third part addresses naturally occurring antioxidants with antiinflammatory activity.
Asunto(s)
Antiinflamatorios/síntesis química , Antioxidantes/síntesis química , Diseño de Fármacos , Especies Reactivas de Oxígeno/metabolismo , Derivados de Alilbenceno , Anisoles/química , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Lactonas/química , Estructura Molecular , Quinonas/química , Especies Reactivas de Oxígeno/antagonistas & inhibidoresRESUMEN
Amine or amide derivatives bearing the 2,6-di-tert-butyl phenol moiety are synthesised. Almost all are antioxidants, reduce acute inflammation and inhibit COX-1 and lipoxygenase activity. The most potent anti-inflammatory, COX-1 inhibitor and antioxidant agent, with low toxicity, is 2,6-di-tert-butyl-4-thiomorpholin-4-ylmethyl-phenol.
Asunto(s)
Antiinflamatorios/síntesis química , Antioxidantes/síntesis química , Hidroxitolueno Butilado/síntesis química , Inflamación/tratamiento farmacológico , Fenoles/química , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antioxidantes/farmacología , Antioxidantes/toxicidad , Hidroxitolueno Butilado/análogos & derivados , Hidroxitolueno Butilado/farmacología , Hidroxitolueno Butilado/uso terapéutico , Carragenina , Ciclooxigenasa 1/metabolismo , Inflamación/inducido químicamente , Inhibidores de la Lipooxigenasa/metabolismo , Masculino , Proteínas de la Membrana/antagonistas & inhibidores , Proteínas de la Membrana/metabolismo , Estructura Molecular , Ratas , Factores de TiempoRESUMEN
We have designed and synthesized a series of novel molecules having a residue of a classical NSAID and an antioxidant moiety, both attached through amide bonds to a known nootropic structure, an L-proline, trans-4-hydroxy-L-proline or DL-pipecolinic acid residue. The compounds were found to retain anti-inflammatory and antioxidant activities, to acquire hypocholesterolemic action, and to possess a greatly reduced gastrointestinal toxicity. The novel molecules could find useful applications, among others, in slowing the progression or delaying the onset of neurodegenerative diseases.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Antioxidantes/farmacología , Artritis/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Ácidos Pipecólicos/farmacología , Prolina/farmacología , Animales , Antiinflamatorios no Esteroideos/síntesis química , Antiinflamatorios no Esteroideos/química , Anticolesterolemiantes/síntesis química , Anticolesterolemiantes/química , Anticolesterolemiantes/farmacología , Antioxidantes/síntesis química , Antioxidantes/química , Colesterol/sangre , Modelos Animales de Enfermedad , Diseño de Fármacos , Evaluación Preclínica de Medicamentos , Femenino , Ácidos Pipecólicos/síntesis química , Ácidos Pipecólicos/química , Prolina/análogos & derivados , Prolina/síntesis química , Ratas , Ratas Endogámicas F344 , Relación Estructura-Actividad , Triglicéridos/sangreRESUMEN
Tolfenamic acid esters with nitrooxyalcohols are synthesized. They are anti-inflammatory agents reducing carrageenan rat paw edema, with low gastrointestinal and general toxicity. In vitro, they are nitric oxide donors, inhibitors of lipoxygenase and cyclooxygenases. A two to three carbon chain between carboxylic and nitric ester groups seems optimal for activity.