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.

Structure-based design of an inhibitor modeled at the substrate active site of aldose reductase / Rastelli, Giulio; P., Vianello; D., Barlocco; Costantino, Luca; G., Cignarella; A., DEL CORSO; U., Mura. - In: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. - ISSN 0960-894X. - STAMPA. - 7:(1997), pp. 1897-1902. [10.1016/S0960-894X(97)00321-1]

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

RASTELLI, Giulio;COSTANTINO, Luca;
1997

Abstract

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.
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1902
Structure-based design of an inhibitor modeled at the substrate active site of aldose reductase / Rastelli, Giulio; P., Vianello; D., Barlocco; Costantino, Luca; G., Cignarella; A., DEL CORSO; U., Mura. - In: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. - ISSN 0960-894X. - STAMPA. - 7:(1997), pp. 1897-1902. [10.1016/S0960-894X(97)00321-1]
Rastelli, Giulio; P., Vianello; D., Barlocco; Costantino, Luca; G., Cignarella; A., DEL CORSO; U., Mura
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/304619
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