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Updated: Dec 31, 2025
A Customizable Approach for the Enzymatic Production and Purification of Diterpenoid Natural Products
Published on: October 4, 2019
Promising Terpenes as Natural Antagonists of Cancer: An In-Silico Approach
Ziyad Tariq Muhseen1,2, Guanglin Li1,2
1Key Laboratory of Ministry of Education for Medicinal Plant Resource and Natural Pharmaceutical Chemistry, Shaanxi Normal University, Xi'an 710062, China.
Abstract:
Overexpression of murine double minute 2 (MDM2) results in the inactivation of p53 and causes cancer which is a leading cause of death in recent era. In recent decades, much attention has been paid to discover potential inhibitors against MDM2 in order to cure cancer. Outcomes from studies proposes that the MDM2 is a hot target to screen potent antagonists. Thus, this study aims at discovering natural compounds using several computational approaches to inhibit the MDM2 and to eliminate p53-MDM2 interaction, which would result in the reactivation of p53 activity. A library of 500 terpenes was prepared and several virtual screening approaches were employed to find out the best hits which could serve as p53-MDM2 antagonists. On the basis of the designed protocol, three terpenes were selected. In the present study, for the stability and validation of selected three protein-ligand complexes 20 ns molecular dynamics simulations and principal component analyses (PCA) were performed. Results found that the selected terpenes hits (3-trans-p-coumaroyl maslinic acid, Silvestrol and Betulonic acid) are potential inhibitors of p53-MDM2 interaction and could serve as potent antagonists.
Insights
Researchers identified natural compounds to inhibit MDM2, a protein linked to cancer. These compounds, including three terpenes, show potential in blocking the p53-MDM2 interaction, which could restore cancer-fighting p53 activity.
Area of Science:
- Biochemistry
- Computational Chemistry
- Pharmacology
Background:
- Overexpression of murine double minute 2 (MDM2) leads to p53 inactivation, a critical factor in cancer development.
- Targeting MDM2 is a promising strategy for cancer therapy due to its role in tumor suppression.
- Restoring p53 activity by inhibiting MDM2 presents a potential therapeutic avenue for various cancers.
Purpose of the Study:
- To discover natural compounds that can inhibit MDM2 and disrupt the p53-MDM2 interaction.
- To identify potential anticancer agents from a library of natural compounds using computational methods.
- To validate the efficacy of identified compounds in inhibiting MDM2-mediated p53 inactivation.
Main Methods:
- Preparation of a library of 500 terpenes for virtual screening.
- Employment of multiple virtual screening approaches to identify potential MDM2 inhibitors.
- Molecular dynamics simulations (20 ns) and principal component analyses (PCA) for stability and validation of protein-ligand complexes.
Main Results:
- Three terpenes, 3-trans-p-coumaroyl maslinic acid, Silvestrol, and Betulonic acid, were identified as potential MDM2 inhibitors.
- The selected terpenes demonstrated the ability to inhibit the p53-MDM2 interaction.
- Molecular dynamics simulations confirmed the stability and potential inhibitory activity of the identified terpene-MDM2 complexes.
Conclusions:
- The identified terpenes are potent antagonists of the p53-MDM2 interaction.
- These natural compounds hold promise as novel therapeutic agents for cancer treatment.
- Further investigation into these terpenes could lead to the development of new anticancer drugs targeting the p53 pathway.
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