Keywords
virtual screening
enrichment study
molecular docking
predictive ADMET
How to Cite
Abstract
Peroxisome proliferated receptors (PPARs) are important targets for drugs used in the treatment of various metabolic disorders. We have reported 4-hydroxy benzylidene derivatives of thiazolidine-2,4-diones with reversed orientation in the active site of PPARγin our earlier communication. With the reversed conformation of TZD, fitting the established pharmacophore was discussed. The current simulation studies revolves around the 2,4-dihydroxy benzylidene derivatives expecting H-bonding interactions similar to Rosiglitazone’s acidic head. The docking protocol was validated by enrichment studies using decoys and actives from DUD. Designed compounds were showing interactions similar to the actives in the top 10%, 5% and 1%. They also exhibited H-bonding interactions similar to their monohydroxy counterparts without any additional H-bonding interactions due to introduction of additional hydroxy functional groups. Predicted ADMET report reveals that 5 molecules show favourable hERG-I and -II properties and nine compounds show best metabolic stability.References
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