NOVEL CHEMOTYPES IN PHARMACOCHEMICAL APPROACHES

Abstract

Diabetes mellitus exacts a huge toll in money and human suffering. At its present rate of increase, within few decades it will be one of the world's commonest diseases and biggest public-health problem, with an estimated minimum of half-a-billion cases. The diabetic, individual is prone to late onset complications that are largely responsible for the morbidity and mortality observed in the patients. It has been demonstrated that the more severe and sustained the degree of hyperglycemia, the more likely it is that the chronic complications of diabetes will develop. Pharmaceutical intervention of hyperglycemia-induced diabetic complications is actively pursued since it is very difficult to maintain normoglycemia by any means in patients with diabetes mellitus. Aldose reductase enzyme (AR, ALR2, E.C. 1.1.1.21) of the polyol metabolic pathway was first found to be implicated in the etiology of secondary complications of diabetes. AR inhibitors (ARIs) have therefore been noted as possible pharmacotherapeutic agents. Although several ARIs have progressed to the clinical level, only one is currently on the market. However, the inhibition of the polyol pathway is considered to be a promising approach to control diabetes complications as well as a number of other pathological conditions like ischemia, abnormal vascular smooth muscle cell proliferation, cancers, and mood disorders. Thus, attention is currently targeted to discover ARIs of distinct chemical structures, being derivatives of neither hydantoin nor carboxylic acid, which are known to cause either toxicity, or posses' narrow spectrum of tissue activity. The focus of this brief overview will aim to support the notion that novel aldose reductase inhibitors with unique physicochemical properties could posses' pharmacotherapeutic potential.