Comparative Design, In Silico Dockingand Predictive ADME/ TOX Properties of Some Novel 2, 4-hydroxy Derivatives of Thiazolidine-2, 4-diones as PPARγ Modulator

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.

Design, Synthesis, Molecular Docking Analysis and Biological Evaluations of 4-[(Quinolin-4-yl)amino]benzamide Derivatives as Novel Anti-Influenza Virus Agents

“…The results of Lipinski’s rule calculation for G01 – G26 included Alop, molecular weight (MW), number of hydrogen-bond acceptors, number of hydrogen-bond donors and number of rotatable bonds ( Table S8 ). It was noticeable that all compounds were in line with the Lipinski’s rule, except for G17 and G18 (the MW of G17 and G18 were more than 500) [ 37 , 38 ].…”

Prediction of Absorption, Distribution, Metabolism, and Excretion Activity of the Components of Madhuca Longifolia and Its Inhibiting Target Molecule

“…Transporters play an important role in the ADME of drugs. Recently, various in vitro and in vivo methods have been established for studying transporter function and drug transporter function [9,27].…”

“…Recent researches on M. longifolia were against diclofenac-induced toxicity in female Wistar albino rabbits, bio fabrication, and characterization of flavonoid loaded Ag, Au, pyrolysis characteristics, fuel properties, and compositional study of M. longifolia butter [4,5]. Absorption, distribution, metabolism, and excretion (ADME) and toxicological profiling are critical parts of any drug development program, and essential for compliance with regulatory guidelines [6][7][8][9]. In this experiment, the ADME properties of each compound were analyzed using SWISS ADME, and the inhibiting target molecule of each compound was found using Swiss TargetPrediction.…”