DOCKING STUDY OF PHYTOCONSTITUENTS OF ASPARAGUS RACEMOSUS FOR ANTICANCER ACTIVITY

Abstract

This present invention investigates the anticancer potential of secondary metabolites from Asparagus racemosus through molecular docking studies targeting Estrogen Receptor a and Aromatase, two key proteins implicated in cancer progression. Phytoconstituents were selected from PubChem, and the protein structures were optimized for docking. Each compound was visualized in ChemDraw and docked using the Glide module in Schrödinger Suite 2020, allowing precise measurements of binding affinities. The study highlights specific interactions between plant compounds and cancer-related proteins, offering valuable insights into natural compounds with strong binding affinity and potential therapeutic applications. This work presents a promising in-silico approach for screening plant-based anticancer agents, paving the way for safer, plant-derived alternatives in cancer treatment.

Specification

Description:FIELD OF INVENTION
The present invention relates to a docking study of phytoconstituents extracted from Asparagus racemosus for potential anticancer activity, focusing on their interactions with cancer-related target proteins to identify promising therapeutic agents.
BACKGROUND OF THE INVENTION
Cancer remains one of the leading causes of morbidity and mortality worldwide, with existing therapies often accompanied by significant side effects and limitations. Conventional chemotherapy and radiation treatments, though widely used, can damage healthy cells along with cancerous ones, leading to adverse reactions and compromised patient quality of life. Additionally, drug resistance is a growing concern, as cancer cells adapt and become less responsive to certain treatments, necessitating the development of new therapeutic agents with novel mechanisms of action.
In recent years, natural products and plant-derived compounds have garnered significant attention as potential sources of anticancer agents due to their diverse chemical structures and biological activities. Asparagus racemosus, commonly known as Shatavari, is a medicinal plant with a long history of use in traditional medicine, attributed to its anti-inflammatory, antioxidant, and immune-modulatory effects. Preliminary research suggests that Asparagus racemosus contains various phytoconstituents, such as saponins, flavonoids, and polyphenols, which may possess anticancer properties. However, the mechanisms by which these phytochemicals exert their anticancer effects remain largely unexplored, and more research is needed to assess their specific interactions with cancer cell targets.
To address this gap, the present invention employs an in-silico docking study to evaluate the binding affinity and potential efficacy of phytoconstituents from Asparagus racemosus against known cancer-related targets. By identifying key interactions between these compounds and cancer cell receptors, this approach aims to isolate specific phytoconstituents that show the greatest promise for inhibiting cancer cell growth. This research can potentially lead to the development of safer, plant-based anticancer therapies with fewer side effects than conventional treatments.
OBJECTS OF THE INVENTION
Some of the objects of the present disclosure, which at least one embodiment herein satisfies, are as follows.
It is an object of the present disclosure to ameliorate one or more problems of the prior art or to at least provide a useful alternative
An object of the present disclosure relates to the in-silico approach for screening plant-based anticancer agents, paving the way for safer, plant-derived alternatives in cancer treatment.
Another object of the present disclosure is to provides a natural, plant-based approach to cancer treatment.
Still another object of the present disclosure is identifies specific Asparagus racemosus compounds with strong anticancer potential.
Another object of the present disclosure is to utilizes in-silico methods, saving time and costs over traditional drug testing.
Still another object of the present disclosure is to targets cancer-related proteins with high precision through molecular docking.
Still another object of the present disclosure is to reduces the need for extensive lab trials in initial screening phases.
Yet another object of the present disclosure is to into safe, non-toxic therapeutic alternatives.
Yet another object of the present disclosure is to helps in understanding compound-protein interactions for drug development.
Yet another object of the present disclosure is to supports the development of eco-friendly, sustainable cancer treatments

Other objects and advantages of the present disclosure will be more apparent from the following description, which is not intended to limit the scope of the present disclosure.

SUMMARY OF THE INVENTION
The following presents a simplified summary of the invention in order to provide a basic understanding of some aspects of the invention. This summary is not an extensive overview of the present invention. It is not intended to identify the key/critical elements of the invention or to delineate the scope of the invention. Its sole purpose is to present some concept of the invention in a simplified form as a prelude to a more detailed description of the invention presented later.

The present invention is generally directed to the anticancer potential of secondary metabolites from Asparagus racemosus using molecular docking techniques. Known for its medicinal properties, Asparagus racemosus contains various phytoconstituents that may inhibit cancer-related targets. The study focuses on key proteins implicated in cancer progression, specifically Estrogen Receptor a (PDB ID 4XI3) and Aromatase (PDB ID 3S79), to identify compounds with strong binding affinities. The selected compounds were retrieved from PubChem, and their molecular structures were optimized for docking through advanced software tools, including ChemDraw Professional for compound visualization and Schrödinger Suite's Protein Preparation Wizard.

An embodiment of the present invention is the docking study employed Schrödinger Suite 2020's Glide module, which enables accurate measurement of binding interactions between the selected phytochemicals and target proteins. Through this approach, the research identified promising interactions between certain compounds and cancer-related proteins, highlighting compounds that may exhibit significant therapeutic effects. Compound 38, in particular, demonstrated notable affinity, suggesting it as a potential candidate for cancer inhibition. This computational framework allows for a streamlined approach to identifying bioactive compounds without the need for extensive laboratory testing.
Another embodiment of the invention is by utilizing the in-silico techniques, this invention provides a foundation for discovering natural anticancer agents derived from Asparagus racemosus. The results not only present a basis for further research into plant-based cancer therapies but also support the development of safe, sustainable, and effective alternatives to synthetic drugs. This study represents a step forward in integrating traditional herbal knowledge with modern computational drug discovery methods, potentially aiding in the development of eco-friendly treatments for cancer.

BRIEF DESCRIPTION OF THE DRAWINGS
Fig 1: 2-D interaction diagram of compound 38 and standard Bazedoxifene
Fig 2: 2-D interaction diagram of compound 38 and standard Letrozole
DETAILED DESCRIPTION OF THE INVENTION
The following description is of exemplary embodiments only and is not intended to limit the scope, applicability or configuration of the invention in any way. Rather, the following description provides a convenient illustration for implementing exemplary embodiments of the invention. Various changes to the described embodiments may be made in the function and arrangement of the elements described without departing from the scope of the invention.
The present invention focuses on evaluating the anticancer potential of secondary metabolites derived from Asparagus racemosus, a plant known for its medicinal properties, through molecular docking studies. Selected phytoconstituents from Asparagus racemosus were retrieved from PubChem and targeted toward specific cancer-related proteins: Estrogen Receptor a (PDB ID 4XI3) and Aromatase (PDB ID 3S79). Each compound was drawn and analyzed using ChemDraw Professional 15.0, while protein structures were optimized through the Schrödinger Suite's Protein Preparation Wizard tool to enhance the docking process. Docking was conducted using the Glide module in Schrödinger Suite 2020, which allowed precise measurements of binding affinity between the selected phytoconstituents and the target proteins. The developed approach enabled an in-depth assessment of the interaction patterns of Asparagus racemosus compounds with key cancer targets, aiding in the identification of phytochemicals with promising anticancer properties. This invention thus provides a novel in-silico framework for assessing plant-based compounds as potential anticancer agents, with applications in developing safer, natural therapeutic alternatives.

EXAMPLE 1: Docking Procedure
The study focused on evaluating secondary metabolites from Asparagus racemosus for their anticancer potential by performing molecular docking studies. Initially, these phytoconstituents were selected from the PubChem database. The target protein structures of Estrogen Receptor a (PDB ID 4XI3) and Aromatase (PDB ID 3S79) were retrieved from the Protein Data Bank (PDB). Each compound was drawn using ChemDraw Professional 15.0 for visualization and further analysis. The protein targets were then prepared using the Schrödinger Suite's Protein Preparation Wizard tool to optimize their structure for docking. Finally, the Glide Docking module within Schrödinger Suite 2020 was used to conduct grid-based ligand docking, allowing for precise measurements of binding affinity between the phytoconstituents and the target proteins.
The docking study results demonstrated that compound 38, identified as Epicatechin, achieved the highest docking score of -11.033 kcal/mol against Estrogen Receptor a (PDB ID 4XI3), indicating a strong binding affinity. Key amino acid residues involved in this interaction included PHE404, ARG394, LEU346, GLY521, and LEU387, with hydrogen bonding observed with GLY521, LEU387, ARG394, and LEU346. The phenol ring of compound 38 interacted notably with PHE404. Comparatively, the docking score of compound 38 was found to be equivalent to that of the standard anticancer drug bazedoxifene, which scored -10.21 kcal/mol, suggesting a similar binding affinity to the target protein. Among the tested compounds, Epicatechin (compound 38) exhibited the most promising inhibition potential against Estrogen Receptor a.
Table 1: Docking score of secondary metabolites that were docked into Estrogenreceptor a (PBD ID 4XI3)
S.No. Ligand Ligand Name Docking Score (kcal/mol)
1. 38 Epicatechin -11.033
2. 1 Shatavarol -11.00
3. 36 Quercetin -10.086
t4. 37 Kaempferol -9.246
5. 40 Luteolin -9.16
6. 39 Apigenin -8.761
7. 32 Glycitein -8.129
8. 33 Biochanin A -7.471
9. 31 Genistein -7.139
10. 35 Formononetin -7.053
11. 34 Daidzein -6.9
12. 24 Sitosterol -4.237
13. 21 Diosgenin -3.82
14. 25 Dolastatin -2.415
15. Bazedoxifene -10.21
Compound 38 showed the best docking score = -7.92 kcal/mol. The crucial amino acid residues contributing to the interaction with compounds 38 SER314, PHE430. Hydrogen bonding was perceived with amino acid residues SER314. Dihydroxy benzene ring was perceived with amino acid residue PHE430.
The molecular docking study revealed that the compound had comparable docking scores to the standard drug letrozole against the aromatase cytochrome P450 (3S79). As a result, these compounds have a target protein affinity similar to letrozole. Among all the designed compounds, 38 showed the highest docking score of -7.92 kcal/mol, which is equivalent to that of letrozole, whose docking score is -7.076 kcal/mol.
Table 2: Docking score of secondary metabolites that were docked into Aromatase (PBD ID 3S79)
S.No. Ligand Ligand Name Docking Score (kcal/mol)
1. 38 Epicatechin -7.92
2. 40 Luteolin -7.832
3. 36 Quercetin -7.651
4. 31 Genistein -7.306
5. 39 Apigenin -7.13
6. 34 Daidzein -6.855
7. 37 Kaempferol -6.695
8. 32 Glycitein -6.397
9. 33 Biochanin A -5.368
10. 35 Formononetin -4.986
11. Letrozole -7.076

While considerable emphasis has been placed herein on the specific features of the preferred embodiment, it will be appreciated that many additional features can be added and that many changes can be made in the preferred embodiment without departing from the principles of the disclosure. These and other changes in the preferred embodiment of the disclosure will be apparent to those skilled in the art from the disclosure herein, whereby it is to be distinctly understood that the foregoing descriptive matter is to be interpreted merely as illustrative of the disclosure and not as a limitation.
, Claims:1. A method for evaluating the anticancer potential of phytoconstituents from Asparagus racemosus, comprising the steps of:
a. selecting secondary metabolites of Asparagus racemosus from a database;
b. retrieving protein structures of Estrogen Receptor a and Aromatase from a protein database;
c. optimizing the protein structures for docking;
d. performing molecular docking of the selected phytoconstituents with the target proteins using a computational docking software;
e. measuring the binding affinity between the phytoconstituents and target proteins to identify potential anticancer agents.
2. The method as claimed in claim 1, wherein the molecular docking is performed using the Glide module of Schrödinger Suite 2020.
3. The method as claimed in claim 1, wherein the secondary metabolites selected from Asparagus racemosus include compounds such as Epicatechin, Quercetin, and Kaempferol.
4. The method as claimed in claim 1, wherein the binding affinity between the phytoconstituents and target proteins is measured in terms of docking score (kcal/mol).

Documents