Structure-based design of an inhibitor modeled at the substrate active site of aldose reductase

Giulio Rastelli, Paola Vianello, Daniela Barlocco, Luca Costantino, Antonella Del Corso, Umberto Mura

Research output: Contribution to journalArticlepeer-review


This study presents the first successful example of structure-based drug design on aldose reductase in the extant literature. Starting from the structure of the modeled complex of aldose reductase with a pyridazinone acetic acid inhibitor that we previously disclosed, using the tools of molecular modeling for structure manipulation and molecular mechanics for energy minimization, we were able to design and synthesize a new analog that showed remarkably improved activity. We hope that a proper account of the most important enzyme-inhibitor interactions revealed by this study mill allow, in the future, the design of new lead compounds having structures unrelated to carboxylic acids.

Original languageEnglish
Pages (from-to)1897-1902
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Issue number14
Publication statusPublished - Jul 22 1997

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science


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