This preprint is under consideration at Journal of Molecular Modeling. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
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Research Article
Iffat Zareen Ahmad
Integral University
Corresponding Author
ORCiD: https://orcid.org/0000-0003-2583-1794
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Phytochemicals derived from Cydonia oblonga have been investigated for their anti-oxidant and anti-cancer activities in many cancer cells lines. The reported bioactive compounds are evaluated in-silico to develop a novel antagonist against pTEN and HBx to target hepatocellular carcinoma. Lower expression of pTEN or higher expression of HBx represents the progression of hepatocellular carcinoma (HCC).
Objective
This research is intended to identify the best candidate which interacts with our target proteins (pTEN and HBx) from the quince seeds by using computational methodologies.
Materials and Methods
The ternary structures of protein and phytochemicals reported in quince like derivatives of caffeoylquinic acid, kaempferol and quercetin, Chrysoeriol, Catechin and other compounds are retrieved from the online databanks. Druglikness analysis and ADMET profiling was done, followed by docking analysis. Lastly, molecular dynamics study was done to determine the complexes stability.
Results
Docking study revealed that CQA derivatives have the significant inhibitory potential of 3CQA and 5CQA with binding affinity of -7.53 and -7.49 against pTEN and -5.94 and -6.01 against HBx in comparison to the standard drug doxorubicin. The average RMSD and RMSF value for protein-ligand complexes were found quite stable comparative to the standard, while parameters like gyration and SASA supports the complexes having the significant binding and stability especially against pTEN.
Conclusion
The results obtained from the evaluation depict 3CQA and 5CQA shows best stability especially with the p10 protein target. Hence, these compounds have to be considered for detailed experimental studies to understand its biological function against HCC.
Keywords
Cydonia oblonga, quince, bioactive compounds, anti-cancer, hepatocarcinoma, molecular docking, molecular dynamics
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This preprint is under consideration at Journal of Molecular Modeling. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Iffat Zareen Ahmad
Integral University
Corresponding Author
ORCiD: https://orcid.org/0000-0003-2583-1794
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Plant Molecular Biology and Genetics
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Phytochemicals derived from Cydonia oblonga have been investigated for their anti-oxidant and anti-cancer activities in many cancer cells lines. The reported bioactive compounds are evaluated in-silico to develop a novel antagonist against pTEN and HBx to target hepatocellular carcinoma. Lower expression of pTEN or higher expression of HBx represents the progression of hepatocellular carcinoma (HCC).
Objective
This research is intended to identify the best candidate which interacts with our target proteins (pTEN and HBx) from the quince seeds by using computational methodologies.
Materials and Methods
The ternary structures of protein and phytochemicals reported in quince like derivatives of caffeoylquinic acid, kaempferol and quercetin, Chrysoeriol, Catechin and other compounds are retrieved from the online databanks. Druglikness analysis and ADMET profiling was done, followed by docking analysis. Lastly, molecular dynamics study was done to determine the complexes stability.
Results
Docking study revealed that CQA derivatives have the significant inhibitory potential of 3CQA and 5CQA with binding affinity of -7.53 and -7.49 against pTEN and -5.94 and -6.01 against HBx in comparison to the standard drug doxorubicin. The average RMSD and RMSF value for protein-ligand complexes were found quite stable comparative to the standard, while parameters like gyration and SASA supports the complexes having the significant binding and stability especially against pTEN.
Conclusion
The results obtained from the evaluation depict 3CQA and 5CQA shows best stability especially with the p10 protein target. Hence, these compounds have to be considered for detailed experimental studies to understand its biological function against HCC.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
This is a list of supplementary files associated with this preprint. Click to download.
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