JPTRM Vol. 5 No. 2 (November 2017)

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https://demodspace.chitkara.edu.in/handle/123456789/133

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Browsing JPTRM Vol. 5 No. 2 (November 2017) by Author "Neelam Sharma"

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    In Silico Designing of Novel Thiazolidine-2-one Derivatives as Dual PDE4/7 Inhibitors for Inflammatory Disorders
    (Chitkara University Publications, 2017-11-02) Ajmer Singh Grewal; Neelam Sharma; Sukhbir Singh; Sandeep Arora
    Phosphodiesterase 4 (PDE4) and phosphodiesterase 7 (PDE7), members of PDE super family, catalyse metabolism of secondary messenger cyclic adenosine monophosphate leading to augmented inflammatory processes in pro-inflammatory and immune-modulatory cells. Dual inhibitors of PDE4/7 are a novel class of drug candidates which can regulate pro-inflammatory as well as function of immune T-cell and are particularly beneficial for the treatment of various inflammatory diseases devoid of unwanted actions. Intense efforts have been directed towards the development of effective dual inhibitors of both PDE4 and PDE7, but not much success has been reported till yet. The aim of present study was to design some newer substituted thiazolidine-2-one derivatives as dual inhibitors of PDE4/7 using structure based rational drug design approach. A new series of thiazolidine-2-one analogues were designed and molecular docking was performed using AutoDock Vina to explore the bonding interactions of the designed molecules with the amino acid residues in the active site of target proteins. The docking study indicated that all the substituted thiazolidine-2-one derivatives have appreciable binding interactions with protein residues of both PDE4 and PDE7. The newly designed compounds could be used as lead molecules for development potent and non-toxic dual inhibitors of PDE4/7 for the management of various inflammatory conditions.
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    Molecular Docking Evaluation of Some Natural Phenolic Compounds as Aldose Reductase Inhibitors for Diabetic Complications
    (Chitkara University Publications, 2017-11-02) Ajmer Singh Grewal; Neelam Sharma; Sukhbir Singh; Sandeep Arora
    The enzyme aldose reductase (AR) is a member of aldoketoreductase super-family which catalyzes the formation of sorbitol from glucose through polyol pathway of glucose catabolism. Reduced sorbitol production via polyol pathway due to AR inhibition is a target of choice for controlling major complications of diabetes. Epalrestat is the only commercially available inhibitor of AR till date,thus, there is a great need to search for more economical, nontoxic and safer inhibitors of AR enzyme. Flavonoids, the polyphenol compounds in plants have been reported for inhibitory effects against AR. The objective of this study is to explore the binding modes of natural phenolic compounds with AR to design safer natural drugs as alternatives to synthetic drugs. We conducted a molecular docking study on some natural phenolic compounds with AR enzyme in complex with the synthetic inhibitor. The overlay of the docked pose of the selected natural phenols with the ARreference inhibitor complex showed that the selected natural compounds have the similar binding pattern with the active site residues of the enzyme as that of co-crystallized inhibitor. The results of docking study showed the best binding affinity of AR with that of 2-(4-hydroxy-3-methoxyphenyl) ethanoic acid and butein, having the lowest binding free energy of –9.8 kcal/mol and–9.7 kcal/mol, respectively. This information can be utilized to design potent, economical and non-toxic natural AR inhibitors from natural phenols for the therapeutics of diabetic complications.