Abstract

Aldose reductase (ALR2) is the enzyme in charge of developing cellular toxicity caused by diabetic hyperglycemia, which in turn leads to the generation of reactive oxygen species triggering oxidative stress. Therefore, inhibiting ALR2 while pursuing a concomitant anti-oxidant activity through dual-acting agents is now recognized as the gold standard treatment for preventing or at least delaying the progression of diabetic complications. Herein we describe a novel series of (E)-benzaldehyde O-benzyl oximes 6a–e, 7a–e, 8a–e, and 9–11 as ALR2 inhibitors endowed with anti-oxidant properties. Inspired by the natural products, the synthesized derivatives are characterized by a different polyhydroxy substitution pattern on their benzaldehyde fragment, which proved crucial for both the enzyme inhibitory activity and the anti-oxidant capacity. Derivatives (E)-2,3,4-trihydroxybenzaldehyde O-(3-methoxybenzyl) oxime (7b) and (E)-2,3,4-trihydroxybenzaldehyde O-(4-methoxybenzyl) oxime (8b) turned out to be the most effective dual-acting products, proving to combine the best ALR2 inhibitory properties with significant anti-oxidant efficacy.

Highlights

  • IntroductionAldose reductase (alditol:NADP+ oxidoreductase, EC 1.1.1.21, AKR1B1, ALR2) is commonly acknowledged as the enzyme in charge of the development of long-term diabetic complications

  • Aldose reductase is commonly acknowledged as the enzyme in charge of the development of long-term diabetic complications

  • Reactions were monitored by thin-layer chromatography (TLC) on silica gel plates containing a fluorescent indicator (Merck Silica Gel 60 F254); spots were detected under UV light

Read more

Summary

Introduction

Aldose reductase (alditol:NADP+ oxidoreductase, EC 1.1.1.21, AKR1B1, ALR2) is commonly acknowledged as the enzyme in charge of the development of long-term diabetic complications. Its inhibition represents the key tool to prevent or at least delay the progression and severity of the pathological changes that diabetics face over time [1]. This consideration has prompted medicinal chemists to design many structurally different compounds as potent ALR2 inhibitors (ARIs), with a goal to develop a gold standard treatment for diabetic diseases affecting the heart, nerve, eye, and kidney. A true and widespread ARI therapy has not yet become a reality despite expectations. Epalrestat (1, Figure 1) is the only drug successfully marketed in Japan, India, and China to treat 4.0/).

Methods
Results
Conclusion
Full Text
Paper version not known

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.