Recent advances in aldose reductase inhibitors: potential agents for the treatment of diabetic complications

Abstract

The development of long-term diabetic complications in diabetes patients is considered to be closely related to hyperglycaemia. Aldose reductase was first found to be implicated in the aetiology of secondary complications of diabetes. A variety of structurally diverse compounds have been observed to inhibit aldose reductase and effective, orally-active inhibitors of the enzyme have been investigated for almost 30 years. Although several of these compounds have progressed to the clinical level, only a few are currently on the market. Furthermore, the number of patents related to aldose reductase inhibitors has declined during recent years, whereas the number for other compounds, such as the inhibitors of the formation of advanced glycated end products and antioxidants, has increased. In this review, recent patents relevant to aldose reductase inhibitors are presented, following a short summary of early works. Lastly, rational approaches to the discovery of aldose reductase inhibitors are briefly reviewed.

Antihyperglycemic Effect of Cephalotaxus sinensis Leaves and GLUT-4 Translocation Facilitating Activity of Its Flavonoid Constituents

“…The aldose reductase inhibitors can effectively prevent and delay diabetic complications, such as diabetic nephropathy, vasculopathy, retinopathy, and peripheral neuropathy. 38,39) Matsuda et al reported that the inhibitory effect of apigenin on aldose reductase, and the IC 50 (concentration of 50% inhibitory percentage) value was 0.58 mM. 40) In the FC, many flavonoids were found involving apigenin, apigenin glycoside.…”

Glucose Tolerance Factor – Insulin Mimetic and Potentiating Agent – A Source for a Novel Anti Diabetic Medication

“…Although treatment with AR inhibitors has been shown to prevent tissue injury in animal models of diabetes, the clinical efficacy of these drugs remains to be established. [20].…”

On the Synthesis of Bioisosters of O‐Benzothiazolyloxybenzoic Acids and Evaluation as Aldose Reductase Inhibitors

“…It is well known from the literature that introduction of a (substituted) benzothiazolyl or a (substituted) benzyl moiety leads to increased aldose reductase inhibition [1,2]. Besides, we became interested in formal replacement of the lipophilic residue.…”

“…However, these inhibitors were withdrawn from clinical trials due to lack of high efficacy or toxicity. To date, the only drug launched on the market is Epalrestat [2]. Another drug, AS-3201, has recently entered phase III trials to study safety and efficacy in the treatment of diabetic sensorimotor polyneuropathy [3].…”