Aldose reductase inhibitors: 2013-present

ABSTRACT

Introduction: Aldose reductase (ALR2) is both the key enzyme of the polyol pathway, whose activation under hyperglycemic conditions leads to the development of chronic diabetic complications, and the crucial promoter of inflammatory and cytotoxic conditions, even under a normoglycemic status. Accordingly, it represents an excellent drug target and a huge effort is being done to disclose novel compounds able to inhibit it.

Areas covered: This literature survey summarizes patents and patent applications published over the last 5 years and filed for natural, semi-synthetic and synthetic ALR2 inhibitors. Compounds described have been discussed and analyzed from both chemical and functional angles.

Expert opinion: Several ALR2 inhibitors with a promising pre-clinical ability to address diabetic complications and inflammatory diseases are being developed during the observed timeframe. Natural compounds and plant extracts are the prevalent ones, thus confirming the use of phytopharmaceuticals as an increasingly pursued therapeutic trend also in the ALR2 inhibitors field. Intriguing hints may be taken from synthetic derivatives, the most significant ones being represented by the differential inhibitors ARDIs. Differently from classical ARIs, these compounds should fire up the therapeutic efficacy of the class while minimizing its side effects, thus overcoming the existing limits of this kind of inhibitors.

KEYWORDS:

• Aldose reductase
• aldose reductase inhibitors
• aldose reductase differential inhibitors
• aldose reductase inhibitor patents
• phytoparmaceuticals
• semi-synthetic inhibitors
• synthetic inhibitors

Article highlights

• Aldose reductase is a cytosolic enzyme involved in biochemical pathways leading to both pathological and resolutive conditions.

• Its Janus-faced character makes the obtainment of active and safe inhibitors highly demanding, thus legitimating the paucity of effective compounds developed to date.

• Natural compounds and plant extracts show ALR2 inhibitory efficacy, with a promising pre-clinical ability to address both diabetic complications and inflammatory diseases.

• Among synthetic inhibitors, the most significant ones are represented by the so-called ARDIs, aldose reductase differential inhibitors.

• ARDIs are intended to target diabetic complications and inflammatory diseases while leaving unaltered the detoxifying role of the enzyme.

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

This paper was not funded.