Potential Mortalin-p53 complex abrogation of ent-kaurane diterpenoids from Croton tonkinensis revealed by homology modeling and docking simulation

Quan Minh PHAM, Hai Viet HA, Nghi Huu DO, Hung Viet DAO, Thu Le Thi VU


Seven ent-kaurane diterpenoids from Croton tonkinensis were tested for cytotoxicity against human HCC HepG2 cell line. The abrogation of mortalin-p53 interaction represent an original anticancer therapeutic approach. Teritary structure of protein mortalin was constructed using Protein Structure Prediction Server and crystal structure of p53 was selected from Protein Data Bank involving mortalin-p53 binding domain. Molecular docking studies revealed that the interaction with protein mortalin is more prominent than p53   compound 5 and 1 as the most two potential mortalin-p53 binding inhibitors based on binding free energy and interacting residues analysis.


Croton tonkinensis, ent-kaurane diterpenoid, cytotoxicity, molecular docking, mortalin-p53

Full Text:



Giang P. M., Jin H. Z., Son P. T., Lee J. H., Hong Y. S., and Lee J. J. - ent-Kaurane Diterpenoids from Croton tonkinensis Inhibit LPS-Induced NF-κB Activation and NO Production, Journal of Natural Products 66 (9) (2003) 1217-1220.

Chi V. V. - Dictionary of Vietnamese Medicinal Plants, Medicine Publishing House: Ho Chi Minh City, 1997.

Kuo P. C., Shen Y. C., Yang M. L., Wang S. H., Thang T. D., Dung N. X., Chiang P. C., Lee K. H., Lee E. J., and Wu T. S. - Crotonkinins A and B and Related Diterpenoids fromCroton tonkinensisas Anti-inflammatory and Antitumor Agents, Journal of Natural Products 70 (12) (2007) 1906-1909.

Sul Y. H., Lee M. S., Cha E. Y., Thuong P. T., Khoi N. M., and Song I. S. - An ent-Kaurane Diterpenoid from Croton tonkinensis Induces Apoptosis by Regulating AMP-Activated Protein Kinase in SK-HEP1 Human Hepatocellular Carcinoma Cells, Biological and Pharmaceutical Bulletin (2013) 158-164.

Thuong P. T., Khoi N. M., Ohta S., Shiota S., Kanta H., Takeuchi K., and Ito F. - ent-Kaurane Diterpenoids from Croton tonkinensis Induce Apoptosis in Colorectal Cancer Cells through the Phosphorylation of JNK Mediated by Reactive Oxygen Species and Dual-Specificity JNK Kinase MKK4, Anti-Cancer Agents in Medicinal Chemistry 14 (7) (2014) 1051-1061.

Ivanov A. A., Khuri F. R., and Fu H. - Targeting protein–protein interactions as an anticancer strategy, Trends in Pharmacological Sciences 34 (7) (2013) 393-400.

Andreeff M., Kelly K. R., Yee K., Assouline S., Strair R., Popplewell L., Bowen D., Martinelli G., Drummond M. W., Vyas P., et al. - Results of the Phase I Trial of RG7112, a Small-Molecule MDM2 Antagonist in Leukemia, Clinical Cancer Research 22 (4) (2015) 868-876.

Wadhwa R., Taira K., and Kaul S. C. - An Hsp70 family chaperone, mortalin/mthsp70/PBP74/Grp75: what, when, and where?, Cell Stress & Chaperones 7 (3) (2002).

Kaul, S. C., Deocaris C. C., and Wadhwa R. - Three faces of mortalin: A housekeeper, guardian and killer, Experimental Gerontology 42 (4) (2007) 263-274.

Yi X., Luk J. M., Lee N. P., Peng J., Leng X., Guan X. Y., Lau G. K., Beretta L., and Fan S. T. - Association of Mortalin (HSPA9) with Liver Cancer Metastasis and Prediction for Early Tumor Recurrence, Molecular & Cellular Proteomics 7 (2) (2008) 315-325.

Kaul S. C., Aida S., Yaguchi T., Kaur K., and Wadhwa R. - Activation of Wild Type p53 Function by Its Mortalin-binding, Cytoplasmically Localizing Carboxyl Terminus Peptides, Journal of Biological Chemistry 280 (47) (2005) 39373-39379.

Lu W. J., Lee N. P., Kaul S. C., Lan F., Poon R. T. P., Wadhwa R., and Luk J. M. - Mortalin–p53 interaction in cancer cells is stress dependent and constitutes a selective target for cancer therapy, Cell Death & Differentiation 18 (6) (2011) 1046-1056.

Deli M. A., Saxena N., Shah N., Singh R., Manjunath K., Uthayakumar M., Kanajuia S. P., Kaul S. C., Sekar K., and Wadhwa R. - Differential Activities of the Two Closely Related Withanolides, Withaferin A and Withanone: Bioinformatics and Experimental Evidences, PLoS ONE 7 (9) (2012).

Mosmann T. - Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays, Journal of Immunological Methods 65 (1-2) (1983) 55-63.

Mittl P. R. E., Chène P., and Grütter M.G. - Crystallization and structure solution of p53 (residues 326–356) by molecular replacement using an NMR model as template, Acta Crystallographica Section D Biological Crystallography 54 (1) (1998) 86-89.


Schrodinger, LLC, The PyMOL Molecular Graphics System, Version 1.8. 2015.

Allouche A. R. - Gabedit-A graphical user interface for computational chemistry softwares, Journal of Computational Chemistry 32 (1) (2011) 174-182.

Utomo D. H., Widodo N., and Rifa’i M. - Identifications small molecules inhibitor of p53-mortalin complex for cancer drug using virtual screening, Bioinformation 8 (9) (2012) 426-429.

Grover A., Priyandoko D., Gao R., Shandilya A., Widodo N., Bisaria V. S., Kaul S. C., Wadhwa R., and Sundar D. - Withanone binds to mortalin and abrogates mortalin–p53 complex: Computational and experimental evidence, The International Journal of Biochemistry & Cell Biology 44 (3) (2012) 496-504.

DOI: https://doi.org/10.15625/2525-2518/58/6A/15602 Display counter: Abstract : 18 views. PDF : 6 views.


  • There are currently no refbacks.

Bioteknologi Agrikultur

Index: Google Scholar; Crossref; VCGate; Asean Citation Index

Published by Vietnam Academy of Science and Technology