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.
| Original language | English |
|---|---|
| Pages (from-to) | 1897-1902 |
| Number of pages | 6 |
| Journal | Bioorganic and Medicinal Chemistry Letters |
| Volume | 7 |
| Issue number | 14 |
| DOIs | |
| Publication status | Published - Jul 22 1997 |
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ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Organic Chemistry
- Drug Discovery
- Pharmaceutical Science
Cite this
Structure-based design of an inhibitor modeled at the substrate active site of aldose reductase. / Rastelli, Giulio; Vianello, Paola; Barlocco, Daniela; Costantino, Luca; Del Corso, Antonella; Mura, Umberto.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 7, No. 14, 22.07.1997, p. 1897-1902.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Structure-based design of an inhibitor modeled at the substrate active site of aldose reductase
AU - Rastelli, Giulio
AU - Vianello, Paola
AU - Barlocco, Daniela
AU - Costantino, Luca
AU - Del Corso, Antonella
AU - Mura, Umberto
PY - 1997/7/22
Y1 - 1997/7/22
N2 - 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.
AB - 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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U2 - 10.1016/S0960-894X(97)00321-1
DO - 10.1016/S0960-894X(97)00321-1
M3 - Article
AN - SCOPUS:0030854601
VL - 7
SP - 1897
EP - 1902
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 14
ER -