In silico Molecular Docking Studies of Quercetin Compound against
Anti-inflammatory and Anticancer Proteins
Parameswari. P1*, Devika. R2
1Research Scholar, Department of Biotechnology, Sathyabama Institute of Science and Technology,
Chennai-600119 Dist- Kancheepuram, India.
2Professor, Department of Biotechnology, Aarupadai Veedu Institute of Technology, Paiyanoor,
Chennai-603104 Dist- Kancheepuram, India.
*Corresponding Author E-mail: eshwari_2007@yahoo.com
ABSTRACT:
Quercetin (a plant flavonoid) having a spot with polyphenol extensively disseminated in nature. Quercetin has aglycone structure and other flavonoid glycosides are rutin and quercetin. The examination displayed the quercetin compound was the best compound exhibiting higher confining imperativeness. In the present examination quercetin was isolated from the leaf concentrate of Artemisia nilagirica (Clarke) Pamp and the concentrate was certified through various instrumental examinations. An undertaking has been made for docking study practices with the extraordinary perceived characteristics MSX 2, HOX A10, HOX A5 and MAPK 14 for quieting proteins and SGK-1, BAX, ZFN 26 and ADM for anticancer. The docking results showed that there exists a coupling relationship between each protein and the goal of ligand-protein docking is to anticipate the overwhelming confining models of a ligand with a protein of known three dimensional structures. Docking considers yielded basic information concerning the presentation of the inhibitors in the coupling pocket of the objective proteins. The present work recognizes the potential remedy that concentrations against the receptor proteins as a characteristic solution to cure inflammation and cancer. The examination reveals that Quercetin can go utilized as medication to fix irritation and dangerous development. Fundamental point of this examination is to limit the dangerous impact of open medications to the common human cell. The examination displayed the Quercetin compound was the best compound appearing limiting imperativeness when differentiated Quercetin and moderating protein MAPK14 receptor leaving - 9.7 kcal/mol and anticancer proteins SGK-1 receptor is - 9.5 kcal/mol of confining essentialness. Taken together our results show that Quercetin may go about as alleviating and anticancer compound by affecting the NF-κB pathway. Further examinations in pre-clinical and clinical examinations are justified to illuminate the helpful capability of Quercetin for clinical use.
KEYWORDS: Auto Dock, Quercetin, apoptotic proteins, anti-inflammatory protein, binding energy.
INTRODUCTION:
As of late, the quantity of studies directed on the utilization of flavonoids in different sectors of the industry is increasing. Thus, the conceivable utilization of these compounds is common because of their antioxidant properties in the fields of food, textiles, leather, metallurgy, medicine and agriculture2.
In this way, Quercetin is a typical hotspot for the sustenance and pharmaceutical industry. Quercetin (3, 5, 7, 3', 4'- pentahydroxyflavone) is delegated a flavonol which is one of the five subclasses and principle dietary flavonoids dispersed in both developed plants and wild plants3. Flavonoids expect a basic occupation in battling various diseases, for instance, quieting, antifungal, antimicrobial, anticonvulsant, antiulcer, antagonistic to filarial, anticancer and malignancy aversion operator activity4,5,6. Many have low poisonous quality in warm blooded animals and some of them are generally utilized in drug for support of narrow respectability. Rutin, 5,7,3',4', tetrahydroxy flavonol 3-rhamnoglucoside and quercetin 5,7,3',4',- tetrahydroxy flavonol are displays mitigating, antihepatotoxic, antiulcer, antiallergic, antiviral activities and some of them gives assurance against cardiovascular mortality7.
Nuclear Docking is a system which predicts the favored acquaintance of one molecule with a second when bound to each other to shape a relentless puzzling. The present examination is in a general sense focusing the hypothetical union of 3-methylquercetin (Isorhamnetin) is an O-methylated flavonol, contain choromone as the essential moiety and found in Tagetes lucida plant utilized as inhibitors of IL-6 protein which is associated with rheumatoid joint inflammation, docking was done in Argus Lab programming8. Flavonoids are compounds with differed chemical structures and are generally found in organic products, vegetables, nuts and seeds. Quercetin and rutin are plentiful in plants and nourishments and show the auxiliary necessities positive to solid cell reinforcement exercises9.
Based upon the lowest binding energy and inhibition constants of terpenoids, and flavonoids acquired through docking thinks about are inspected for their in vitro acetylcholine esterase inhibitory movement utilizing tacrine as standard10. Alcoholic concentrate of leaves of Mussaenda frondosa Linn. (Rubiaceae) and its disconnected compound quercetin were assessed for wound recuperating action11,12. Quercetin is the aglycone type of various other flavonoid glycosides found in citrus foods grown from the ground13.
Quercetin is basically a flavanol, it is a plant determined flavonoid that is found in various products of the soil and has different defensive capacities14. To assess the similarity of quercetin with different pharmaceutical excipients to be utilized in the nanoparticle details using the diverse expository systems15. Quercetin (3, 5, 7, 3′, 4′-pentahydroxylflavone) has a wide scope of pharmacological properties like enemy of oxidative, against leishmanial, antiviral, calming and hostile to proliferative16. AutoDock is programming discharged under General Public License with a couple of restrictions on business or nonbusiness use, or on the backup attempts to perform sub-atomic docking17. Flavones and flavonoids, especially Quercetin, are known to uncover an essential procedure of cytotoxicity against refined human cells by expanding the quantity of intracellular reactive oxygen species18.
Quercetin has been reported as a long-lasting anti-inflammatory substance with strong anti-inflammatory properties19,40. It has anti-inflammatory potential that can be communicated on various cell types, both in creature models and in human models20,21. Quercetin is known to have both a pole cell settling and gastrointestinal cytoprotective activity22 and it can likewise apply an adjusting, biphasic and managing activity on aggravation and immunity21. What's more, quercetin immunosuppressively affects dendritic cell function23.
MATERIALS AND METHODS:
Auto Dock:
Auto Dock Vina is a suite of computerized docking devices like Auto Dock. It is intended to predict how little atoms, for example, substrates or drug candidates, bind to a receptor of known 3D structure. Auto Dock really comprises of two principle programs: Auto Dock plays out the docking of the ligand to a lot of grids describing the target protein, Auto Grid pre-computes these grids. In addition to using them for docking, the nuclear liking grids can be imagined. This can help, for instance, to direct natural manufactured scientific experts configuration better fasteners. A graphical UI called ADT (Auto dock Tools) has been utilized sets up which bonds that will treat as rotatable in the ligand. This empowers to investigate the docking association between the medication (ligand) and the medication target (receptor) in silico. The Auto dock apparatus has been utilized for contemplating the connection among Quercetin and Anti-inflammatory and Anticancer Proteins.
Anti-inflammatory Proteins:
1. Msx2 - Homeodomain interpretation calculate that controls hardening calvarial bone of the creating skull. This recommends Msx2 suppresses transcription via protein-protein cooperation with components of the transcriptional machinery24.
2. HOXA10 - Homeo protein HOX-A10 is a human protein which is encoded by HOX-A10 quality and they are found in groups as A, B, C and D on four separate chromosomes25.
3. HOXA5 Is a human protein encoded by HOXA5 quality and found as clusters named A, B, C and D on four separate chromosomes. Methylation of this quality up regulates the tumour silencer P53 and assumes an essential job in tumorigenesis26.
4. MAPK14 - Mitogen Activated Protein Kinase 14 likewise called as P38 which encodes MAPK 14 quality and it is also called pressure initiated serine/threonine explicit kinases (SAPKs). They are recognized in actuated safe cells macrophages with a fundamental job in incendiary cytokine enlistment (Tumour Necrosis Factor alpha)38.
Anticancer Proteins:
1. SGK1 Serum and Glucocorticoid managed Kinase isoform 1 (referred to as SGK 1) is a positive administrative of ENa C. SGK expression is switched on in response to a number of stimuli and integrates information from a several pathways including the insulin, mineralocorticoid and Camp signalling pathway27.
2. BAX Apoptosis controller BAX is known as Bcl-2 protein 4 which encodes by BAX qualities and they have a place with Bcl-2 quality family. Bcl-2 work as an apoptotic activator and it is directed by the tumour silencer p5328.
3. ZNF 26 The individuals from the human Zinc finger Kruppel family. ZNF 26 (KOX 20) have been localised by somatic cell hybrid analysis in situ chromosomal hybrodisation29.
4. ADM - Adrenomedullin Protein is a vasodilator peptide hormone and the fundamental capacity potentiates the capacity of carcinogenic cells and broadens their blood supply and empowers further cell proliferation30.
Preparing the Protein:
Protein Data Bank (PDB) documents can have an assortment of potential issues that should be revised before they can be utilized in AutoDock. These potential issues incorporate missing atoms, included waters, more than one atom, chain breaks, alternate locations etc. The water particles must be expelled and polar hydrogen atoms must be included and spare in "pdb" format. The receptor document utilized via AutoDockVina must be in "pdbqt" design which is pdb in addition to 'q' charge and 't' AutoDock molecule types which recognizes the distinctive kinds of atoms.
The design record tells AutoDock Vina which has the details need by the Vina to run docking investigation, for example, the information document names, grid box parameters which gives the details of the search space: by adjusting the directions of the matrix put away bring the receptor and ligand into the grid area, yield of the docked postures, thoroughness, number of modes to be created in a typical content.
Running AutoDock Vina Program:
AutoDock Vina is executed utilizing order brief in Windows. Browse through the area of the receptor and the ligand records in pdbqt design. The areas are determined in the vina.exe file followed by the design document name.
RESULTS AND DISCUSSION:
In the present study, docking results revealed the binding interactions between the Quercetin with 4 anti-inflammatory and 4 anticancer proteins where, in different docking routines, all showed a favorable binding energy greater than -9.5 kcal/mol in SGK1, binding energy is greater than -9.7 kcal/mol in MAPK 14 as shown in the Table 1. The rest of the proteins showed binding energy ranges from -6.6 to -9.5 kcal/mol. The Docking of ligands with that of receptors is done by utilizing ADM and the outcomes were imagined by utilizing Pymol (Figure 1 and 2).
Anti-inflammatory proteins ZNF 26 showed least minimum binding energy with -6.6 kcal/mol and HOX A5 is -7.6Kcal/ mol showed least minimum binding energy in anti-inflammatory proteins as shown in Table 1 and Figure 1. This shows that Quercetin binds to anti-inflammatory protein receptors and the docked conformation has high energy and hence stable. Ligand-protein affinity for alkaloids was found to be low (-7.9 kcal/mol as binding energy in ADM) excepting MAPK14, which demonstrated to achieve an important strong affinity with -9.7 kcal/mol against inflammatory protein receptors.
While in the case of anticancer proteins SGK-1 alone showed higher binding affinity leaving -9.5 kcal/mol. when compared to other proteins like BAX, ZNF 26 and ADM as shown in the Table 1 and Figure 2. The selected Quercetin compound showed binding energy ranging between -6.6 to -9.5 kcal/mol in anticancer proteins and -7.6 to -9.7 kcal/mol which proved that the compound possess potential soluble epoxide hydrolase enzyme inhibitory binding sites and the soluble epoxide hydrolase would effectively increase the in vivo concentration of epoxyeicosatrienoic acid thereby proving to be useful in the treatment of hypertension, inflammation and other disorders31.
Similar type of studies were performed with fucoidan compound against HepG-2 cell line proteins32, kappa-carrragenan present in Kappaphycus alvarezii against InhA enzyme33, quercetin compound against HeLa cell line proteins34, resveratrol compound against KB cell line proteins35, stearic acid against transferrin and plasminogen proteins present on HepG-2 cells present in Cardiospermum halcacabum36 and rutin compound against apoptotic proteins.
Docking simulations with Msx 2, HOXA10, HOXA5, SGK1, BAX, ZNF 26 and ADM-bound ligand Quercetin did not higher binding energy when compared to MAPK14 protein receptor this may be due to smaller catalytic site37, as shown in Table 1 and Figure 1 and 2. The present work recognizes the potential medication that focuses against the receptor proteins as a characteristic solution to cure inflammation and cancer. The study reveals that Quercetin can go utilized as medication to cure inflammation and cancer. Main aim of this study is to limit the harmful impact of accessible medications to the normal human cell. The study demonstrated the Quercetin compound was the best compound indicating higher binding energy when compared Quercetin with anti-inflammatory protein MAPK14 receptor leaving -9.7 kcal/mol and anticancer proteins SGK-1 receptor is -9.5 kcal/mol of binding energy. Taken together from the results show that Quercetin acts as anti-inflammatory and anticancer compound by affecting the NF-κB pathway. Further analyses in pre-clinical and clinical studies are warranted to clarify the therapeutic potential of Quercetin for clinical use.
Fig. 1: Structural based docking of Quercetin with Anti-inflammatory proteins such as MSX 2 (1), HOXA10 (2), HOXA5 (3) and MAPK14 (4)
Fig. 2: Structural based docking of identifying compounds of Quercetin with Anticancer proteins such as SGK1 (1), BAX (2), ZFN 26(3) and ADM (4)
Table 1: Binding energies of Anti-inflammatory and Anticancer proteins with Quercetin
|
Anti-Inflammatory Proteins |
Anticancer Proteins |
||
|
Receptor |
Binding Energy (kcal/mol) |
Receptor |
Binding Energy (kcal/mol) |
|
MSX2 |
-7.9 |
SGK-1 |
-9.5 |
|
HOXA10 |
-7.8 |
BAX |
-8.9 |
|
HOXA5 |
-7.6 |
ZnF 26 |
-6.6 |
|
MAPK14 |
-9.7 |
ADM |
-7.9 |
CONCLUSION:
Docking simulation method was utilized for fundamental investigation of the potential molecular target for the revealed anticancer operator. The investigation of the docked ligand allowed setting up the coupling method of compound involved in this study and confirming the role as anti-inflammatory and anticancer agent. Despite the fact that further role of the compound and its careful component of activity stay to be investigated, it very well may be proposed that compound can be considered as a conceivable restorative operator against irritation and malignancy. Consequently from the molecular docking through in silico examination of Quercetin against inflammatory and apoptotic proteins and it was inferred that Quercetin could be considered as a lead compound. Further investigations are important to chemical entity for the counteractive action and treatment of aggravation and malignancy.
CONFLICT OF INTEREST:
The authors declare no conflict of interest.
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Received on 07.04.2019 Modified on 16.05.2019
Accepted on 18.06.2019 © RJPT All right reserved
Research J. Pharm. and Tech. 2019; 12(11):5305-5309.
DOI: 10.5958/0974-360X.2019.00919.3