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Progresses in the pursuit of aldose reductase inhibitors: the structure-based lead optimization step

Anna Ramunno1, Sandro Cosconati, Stefania Sartini

  • 1Dipartimento di Scienze Farmaceutiche, Università di Salerno, Via Ponte Don Melillo 11c, 84084 Fisciano, Italy.

European Journal of Medicinal Chemistry
|March 23, 2012
PubMed

Insights

Novel aldose reductase (ALR2) inhibitors were developed to treat diabetic complications and inflammatory diseases. These new compounds show promising low micromolar/submicromolar activities, offering potential therapeutic avenues beyond diabetes.

Area of Science:

  • Biochemistry
  • Medicinal Chemistry
  • Pharmacology

Background:

  • Aldose reductase (ALR2) is implicated in diabetic complications.
  • ALR2 inhibitors, like fidarestat, show potential against inflammatory diseases and cancer.
  • Fidarestat is in Phase III trials for diabetic neuropathy and is safe.

Purpose of the Study:

  • To discover novel, potent aldose reductase (ALR2) inhibitors.
  • To explore new therapeutic strategies for diabetes and inflammatory conditions.
  • To optimize a virtual screening-derived ALR2 inhibitor (S12728).

Main Methods:

  • Rational receptor-based lead optimization.
  • Chemical synthesis of new compounds.
  • In vitro activity assessment of synthesized compounds.

Main Results:

  • Several new ALR2 inhibitors were designed and synthesized.
  • Compounds demonstrated low micromolar and submicromolar activities.
  • Optimization efforts yielded potent inhibitory compounds.

Conclusions:

  • Novel ALR2 inhibitors with significant potency were discovered.
  • These compounds offer potential for treating diabetic complications and inflammatory diseases.
  • The findings support the development of new therapeutic approaches.

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