An Old NSAID Revisited: Crystal Structure of Aldose Reductase in Complex with Sulindac at 1.0 Å Supports a Novel Mechanism for its Anticancer and Antiproliferative Effects

Steuber, H.

doi:10.1002/cmdc.201100374

Cited by 6 publications

(1 citation statement)

References 26 publications

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“…Thus the much weaker binding affinity of indomethacin to AR than SLD is very reasonable. As the present paper was being prepared for publication, a structure of AR in complex with SLD was published by Steuber [38]. Although the two studies are generally in agreement, our paper provides a more detailed enzyme/molecular basis for understanding of the AR inhibitory mechanism of sulindac, its metabolites and its analog tolmetin.…”

Section: A Unique P-p Stacking Favored By a Distinct Scaffold Of Sld mentioning

confidence: 53%

The molecular basis for inhibition of sulindac and its metabolites towards human aldose reductase

et al. 2011

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Edited by Stuart FergusonKeywords: Sulindac Metabolite Tolmetin Aldose reductase Crystal structure a b s t r a c t Sulindac (SLD) exhibits both the highest inhibitory activity towards human aldose reductase (AR) among popular non-steroidal anti-inflammatory drugs and clear beneficial clinical effects on Type 2 diabetes. However, the molecular basis for these properties is unclear. Here, we report that SLD and its pharmacologically active/inactive metabolites, SLD sulfide and SLD sulfone, are equally effective as un-competitive inhibitors of AR in vitro. Crystallographic analysis reveals that p-p stacking favored by the distinct scaffold of SLDs is pivotal to their high AR inhibitory activities. These results also suggest that SLD sulfone could be a potent lead compound for AR inhibition in vivo.

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Section: A Unique P-p Stacking Favored By a Distinct Scaffold Of Sld mentioning

confidence: 53%

The molecular basis for inhibition of sulindac and its metabolites towards human aldose reductase

et al. 2011

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Challenges in docking 2′-hydroxy and 2′,4′-dihydroxychalcones into the binding site of ALR2

et al. 2012

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Pharmacophore and docking-based hierarchical virtual screening for the designing of aldose reductase inhibitors: synthesis and biological evaluation

et al. 2016

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An Old NSAID Revisited: Crystal Structure of Aldose Reductase in Complex with Sulindac at 1.0 Å Supports a Novel Mechanism for its Anticancer and Antiproliferative Effects

Cited by 6 publications

References 26 publications

The molecular basis for inhibition of sulindac and its metabolites towards human aldose reductase

The molecular basis for inhibition of sulindac and its metabolites towards human aldose reductase

Challenges in docking 2′-hydroxy and 2′,4′-dihydroxychalcones into the binding site of ALR2

Pharmacophore and docking-based hierarchical virtual screening for the designing of aldose reductase inhibitors: synthesis and biological evaluation

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