Efforts Towards Repurposing of Antioxidant Drugs and Active Compounds for Multiple Sclerosis Control.

Multiple Sclerosis (MS) is a degenerative disorder of the central nervous system (CNS) with complicated etiology that has not been clearly analyzed until nowadays. Apart from anti-inflammatory, immune modulatory and symptomatic treatments, which are the main tools towards MS control, antioxidant molecules may be of interest. Oxidative stress is a key condition implicated in the disease progression. Reactive species production is associated with immune cell activation in the brain as well as in the periphery, accounting for demyelinating and axonal disruptive processes. This review refers to research articles, of the last decade. It describes biological evaluation of antioxidant drugs, and molecules with pharmaceutical interest, which are not designed for MS treatment, however they seem to have potency against MS. Their antioxidant effect is accompanied, in most of the cases, by anti-inflammatory, immune-modulatory and neuroprotective properties. Compounds with such characteristics are expected to be beneficial in the treatment of MS, alone or as complementary therapy, improving some clinical and mechanistic aspects of the disease. This review also summarizes some of the pathobiological characteristics of MS, as well as the role of oxidative stress and inflammation in the progression of neurodegeneration. It presents known drugs and bioactive compounds with antioxidant, and in many cases, pleiotropic activity that have been tested for their efficacy in MS progression or the experimentally induced MS. Antioxidants may offer reduction or prevention of the disease symptoms and progression. Thus, their results may, combined with already applied treatments, be beneficial for the development of new molecules or the repurposing of drugs and supplements that are used with other indication so far.

Lipoic acid. Kinetics and pluripotent biological properties and derivatives.

Lipoic acid (LA) is globally known and its supplements are widely used. Despite its importance for the organism it is not considered a vitamin any more. The multiple metabolic forms and the differences in kinetics (absorption, distribution and excretion), as well as the actions of its enantiomers are analysed in the present article together with its biosynthetic path. The proteins involved in the transfer, biotransformation and activity of LA are mentioned. Furthermore, the safety and the toxicological profile of the compound are commented, together with its stability issues. Mechanisms of lipoic acid intervention in the human body are analysed considering the antioxidant and non-antioxidant characteristics of the compound. The chelating properties, the regenerative ability of other antioxidants, the co-enzyme activity and the signal transduction by the implication in various pathways will be discussed in order to be elucidated the pleiotropic effects of LA. Finally, lipoic acid integrating analogues are mentioned under the scope of the multiple pharmacological actions they acquire towards degenerative conditions.

Design and study of some novel ibuprofen derivatives with potential nootropic and neuroprotective properties.

Six novel ibuprofen derivatives and related structures, incorporating a proline moiety and designed for neurodegenerative disorders, are studied. They possess anti-inflammatory properties and three of them inhibited lipoxygenase. One compound was found to inhibit cyclooxygenase (COX)-2 production in spleenocytes from arthritic rats. The HS-containing compounds are potent antioxidants and one of them protected against glutathione loss after cerebral ischemia/reperfusion. They demonstrated lipid-lowering ability and seem to acquire low gastrointestinal toxicity. Acetylcholinesterase inhibitory activity, found in two of these compounds, may be an asset to their actions.

Synthesis and pharmacochemical study of novel polyfunctional molecules combining anti-inflammatory, antioxidant, and hypocholesterolemic properties.

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.