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Pharmacophore Modeling and Molecular Docking Studies on Pinus roxburghii as a Target for Diabetes Mellitus.

Kaushik P, Lal Khokra S, Rana AC, Kaushik D - Adv Bioinformatics (2014)

Bottom Line: From the results of docking score values on different receptors for antidiabetic activity, it is observed that constituents, namely, secoisoresinol, pinoresinol, and cedeodarin, showed the best docking results on almost all the receptors, while the most significant results were observed on AR.In our molecular docking studies, the active constituent, secoisoresinol, has also shown hydrogen bonding with His 110 residue which is a part of the pharmacophore.The docking results have given better insights into the development of better aldose reductase inhibitor so as to treat diabetes related secondary complications.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra 136119, India.

ABSTRACT
The present study attempts to establish a relationship between ethnopharmacological claims and bioactive constituents present in Pinus roxburghii against all possible targets for diabetes through molecular docking and to develop a pharmacophore model for the active target. The process of molecular docking involves study of different bonding modes of one ligand with active cavities of target receptors protein tyrosine phosphatase 1-beta (PTP-1β), dipeptidyl peptidase-IV (DPP-IV), aldose reductase (AR), and insulin receptor (IR) with help of docking software Molegro virtual docker (MVD). From the results of docking score values on different receptors for antidiabetic activity, it is observed that constituents, namely, secoisoresinol, pinoresinol, and cedeodarin, showed the best docking results on almost all the receptors, while the most significant results were observed on AR. Then, LigandScout was applied to develop a pharmacophore model for active target. LigandScout revealed that 2 hydrogen bond donors pointing towards Tyr 48 and His 110 are a major requirement of the pharmacophore generated. In our molecular docking studies, the active constituent, secoisoresinol, has also shown hydrogen bonding with His 110 residue which is a part of the pharmacophore. The docking results have given better insights into the development of better aldose reductase inhibitor so as to treat diabetes related secondary complications.

No MeSH data available.


Related in: MedlinePlus

Pharmacophore model of 1US0.
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fig2: Pharmacophore model of 1US0.

Mentions: The traditional medicinal system has plenty of opportunities, which are however needed to be explored till date for the treatment of many ailments [33]; if one can employ the modern computational chemistry tools for exploring the potential of the traditional medicinal system, then astonishing results can be received. Similar studies have been taken away in the past by many scientists where bioactive compounds are docked on particular receptor to evaluate its affinity [34–36]. In our work, we used two approaches of structure based drug designing, namely, molecular docking and pharmacophore modeling for measuring the potential antidiabetic components and their mechanism of activity. The primary aim of selecting the four different receptors was to distinguish the major pathway through which Pinus roxburghii exhibits its antidiabetic potential. From our docking results we found that it was aldose reductase on which active constituents from Pinus roxburghii were found to be most active. The role of aldose reductase inhibitors in diabetes has been corroborated by many researchers [37]. Further, our docking on the enzyme 1US0 (aldose reductase) revealed that secoisoresinol, pinoresinol, and cedeodarin have the highest affinity for AR. Our results were validated by generations of the pharmacophore model which predicts Tyr48 and His 110 as an indispensable essential for the formation of H-bonding with ligand (Figure 2). In our molecular docking simulation on 1US0, we found that internal ligand is interacting with Tyr 48 whereas secoisoresinol which has the highest MolDock score has interaction with His 110; this data is well correlated with the pharmacophore model.


Pharmacophore Modeling and Molecular Docking Studies on Pinus roxburghii as a Target for Diabetes Mellitus.

Kaushik P, Lal Khokra S, Rana AC, Kaushik D - Adv Bioinformatics (2014)

Pharmacophore model of 1US0.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4120483&req=5

fig2: Pharmacophore model of 1US0.
Mentions: The traditional medicinal system has plenty of opportunities, which are however needed to be explored till date for the treatment of many ailments [33]; if one can employ the modern computational chemistry tools for exploring the potential of the traditional medicinal system, then astonishing results can be received. Similar studies have been taken away in the past by many scientists where bioactive compounds are docked on particular receptor to evaluate its affinity [34–36]. In our work, we used two approaches of structure based drug designing, namely, molecular docking and pharmacophore modeling for measuring the potential antidiabetic components and their mechanism of activity. The primary aim of selecting the four different receptors was to distinguish the major pathway through which Pinus roxburghii exhibits its antidiabetic potential. From our docking results we found that it was aldose reductase on which active constituents from Pinus roxburghii were found to be most active. The role of aldose reductase inhibitors in diabetes has been corroborated by many researchers [37]. Further, our docking on the enzyme 1US0 (aldose reductase) revealed that secoisoresinol, pinoresinol, and cedeodarin have the highest affinity for AR. Our results were validated by generations of the pharmacophore model which predicts Tyr48 and His 110 as an indispensable essential for the formation of H-bonding with ligand (Figure 2). In our molecular docking simulation on 1US0, we found that internal ligand is interacting with Tyr 48 whereas secoisoresinol which has the highest MolDock score has interaction with His 110; this data is well correlated with the pharmacophore model.

Bottom Line: From the results of docking score values on different receptors for antidiabetic activity, it is observed that constituents, namely, secoisoresinol, pinoresinol, and cedeodarin, showed the best docking results on almost all the receptors, while the most significant results were observed on AR.In our molecular docking studies, the active constituent, secoisoresinol, has also shown hydrogen bonding with His 110 residue which is a part of the pharmacophore.The docking results have given better insights into the development of better aldose reductase inhibitor so as to treat diabetes related secondary complications.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra 136119, India.

ABSTRACT
The present study attempts to establish a relationship between ethnopharmacological claims and bioactive constituents present in Pinus roxburghii against all possible targets for diabetes through molecular docking and to develop a pharmacophore model for the active target. The process of molecular docking involves study of different bonding modes of one ligand with active cavities of target receptors protein tyrosine phosphatase 1-beta (PTP-1β), dipeptidyl peptidase-IV (DPP-IV), aldose reductase (AR), and insulin receptor (IR) with help of docking software Molegro virtual docker (MVD). From the results of docking score values on different receptors for antidiabetic activity, it is observed that constituents, namely, secoisoresinol, pinoresinol, and cedeodarin, showed the best docking results on almost all the receptors, while the most significant results were observed on AR. Then, LigandScout was applied to develop a pharmacophore model for active target. LigandScout revealed that 2 hydrogen bond donors pointing towards Tyr 48 and His 110 are a major requirement of the pharmacophore generated. In our molecular docking studies, the active constituent, secoisoresinol, has also shown hydrogen bonding with His 110 residue which is a part of the pharmacophore. The docking results have given better insights into the development of better aldose reductase inhibitor so as to treat diabetes related secondary complications.

No MeSH data available.


Related in: MedlinePlus