Prospects for the introduction of targeted antioxidant drugs for the prevention and treatment of diseases related to free radical pathology

ABSTRACT

Introduction: Oxidative stress toxicity (OST) has been implicated in almost all pathological conditions. Despite the widespread use of natural antioxidants, no pharmaceutical antioxidants have yet been developed or prescribed in medical practise. Antioxidant drugs such as Deferiprone and N-acetylcysteine can target essential pathways of OST in many pathological conditions. The pharmacological parameters required by antioxidant drugs in relation to the OST target characteristics include the determination of the therapeutic index, ADMET and drug interactions. Antioxidant drug development efforts are currently targeting the treatment of severe diseases with no proven effective therapies.

Areas covered: This article addresses the damaging effects of OST, prospects for the development of pharmaceutical antioxidants and clinical studies using other drugs with antioxidant potential.

Expert opinion: Effective antioxidant therapeutic strategies should include the design of protocols for the inhibition of OST through iron chelation, administration of synthetic and natural antioxidants and enhancement of the antioxidant defences by increasing the production of endogenous antioxidants and activation of antioxidant mechanisms. Different therapeutic strategies apply in the use of antioxidant drugs for one or more targets, for prevention, treatment, or of post-treatment effects and for systematic, long-term or short-term applications. The design of new antioxidant drugs and effective protocols which can include Deferiprone and N-acetylcysteine combinations, could lead to the development of a new class of therapeutics for clinical use.

KEYWORDS:

• Iron
• chelators
• iron overload
• non-iron loaded diseases
• free radicals
• oxidative stress
• thalassaemia
• cancer
• deferiprone
• N-acetylcysteine

Article Highlights

• Optimal antioxidant therapies in pathological conditions could be designed based on the identification and characterisation of the oxidative stress toxicity target and the selection of the appropriate antioxidant protocol with the maximum efficacy.

• Effective antioxidant therapeutic strategies should target all the components and aspects of oxidative stress toxicity including the source(s), where chelation especially of iron is necessary.

• The unique properties of deferiprone, such as the inhibition of iron and copper catalytic formation of free radicals and the ability to enter almost all cell types at effective therapeutic concentrations could have a use as a universal antioxidant therapeutic.

• Combination of antioxidants targeting all aspects of oxidative stress toxicity is likely to have a better impact than monotherapy on the therapeutic outcome of clinical conditions related to free radical pathology.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

The work of the authors is supported by research funds from the Postgraduate Research Institute of Science, Technology, Environment and Medicine, Limassol, Cyprus.