Diosgenin and Monohydroxy Spirostanol from <i>Prunus amygdalus var amara</i> Seeds as Potential Suppressors of EGFR and HER2 Tyrosine Kinases: A Computational Approach
Cancer continues to be leading cause of death globally, with nearly 7 million deaths per year. Despite significant progress in cancer research and treatment, there remain several challenges to overcome, including drug resistance, the presence of cancer stem cells, and high interstitial fluid pressur...
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MDPI AG
2023-05-01
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| Online Access: | https://www.mdpi.com/1424-8247/16/5/704 |
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| author | Mohammed Helmy Faris Shalayel Ghassab M. Al-Mazaideh Abdulkareem A. Alanezi Afaf F. Almuqati Meshal Alotaibi |
| author_facet | Mohammed Helmy Faris Shalayel Ghassab M. Al-Mazaideh Abdulkareem A. Alanezi Afaf F. Almuqati Meshal Alotaibi |
| author_sort | Mohammed Helmy Faris Shalayel |
| collection | DOAJ |
| description | Cancer continues to be leading cause of death globally, with nearly 7 million deaths per year. Despite significant progress in cancer research and treatment, there remain several challenges to overcome, including drug resistance, the presence of cancer stem cells, and high interstitial fluid pressure in tumors. To tackle these challenges, targeted therapy, specifically targeting HER2 (Human Epidermal Growth Factor Receptor 2) as well as EGFR (Epidermal Growth Factor Receptor), is considered a promising approach in cancer treatment. In recent years, phytocompounds have gained recognition as a potential source of chemopreventive and chemotherapeutic agents in tumor cancer treatment. Phytocompounds are compounds derived from medicinal plants that have the potential to treat and prevent cancer. This study aimed to investigate phytocompounds from <i>Prunus amygdalus var amara</i> seeds as inhibitors against EGFR and HER2 enzymes using in silico methods. In this study, fourteen phytocompounds were isolated from <i>Prunus amygdalus var amara</i> seeds and subjected to molecular docking studies to determine their ability to bind to EGFR and HER2 enzymes. The results showed that diosgenin and monohydroxy spirostanol exhibited binding energies comparable to those of the reference drugs, tak-285, and lapatinib. Furthermore, the drug-likeness and ADMET predictions, performed using the admetSAR 2.0 web-server tool, suggested that diosgenin and monohydroxy spirostanol have similar safety and ADMET properties as the reference drugs. To get deeper insight into the structural steadiness and flexibility of the complexes formed between these compounds and theEGFR and HER2 proteins, molecular dynamics simulations were performed for 100 ns. The results showed that the hit phytocompounds did not significantly affect the stability of the EGFR and HER2 proteins and were able to form stable interactions with the catalytic binding sites of the proteins. Additionally, the MM-PBSA analysis revealed that the binding free energy estimates for diosgenin and monohydroxy spirostanol is comparable to the reference drug, lapatinib. This study provides evidence that diosgenin and monohydroxy spirostanol may have the potential to act as dual suppressors of EGFR and HER2. Additional in vivo and in vitro research are needed to certify these results and assess their efficacy and safety as cancer therapy agents. The experimental data reported and these results are in agreement. |
| first_indexed | 2024-03-11T03:25:44Z |
| format | Article |
| id | doaj.art-af6cbde1c8064f7caaf4872269f444d0 |
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| language | English |
| last_indexed | 2024-03-11T03:25:44Z |
| publishDate | 2023-05-01 |
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| spelling | doaj.art-af6cbde1c8064f7caaf4872269f444d02023-11-18T02:48:43ZengMDPI AGPharmaceuticals1424-82472023-05-0116570410.3390/ph16050704Diosgenin and Monohydroxy Spirostanol from <i>Prunus amygdalus var amara</i> Seeds as Potential Suppressors of EGFR and HER2 Tyrosine Kinases: A Computational ApproachMohammed Helmy Faris Shalayel0Ghassab M. Al-Mazaideh1Abdulkareem A. Alanezi2Afaf F. Almuqati3Meshal Alotaibi4Department of Pharmacy Practice, College of Pharmacy, University of Hafr Al Batin, Hafr Al Batin 31991, Saudi ArabiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, University of Hafr Al Batin, Hafr Al Batin 31991, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, University of Hafr Al Batin, Hafr Al Batin 31991, Saudi ArabiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, University of Hafr Al Batin, Hafr Al Batin 31991, Saudi ArabiaDepartment of Pharmacy Practice, College of Pharmacy, University of Hafr Al Batin, Hafr Al Batin 31991, Saudi ArabiaCancer continues to be leading cause of death globally, with nearly 7 million deaths per year. Despite significant progress in cancer research and treatment, there remain several challenges to overcome, including drug resistance, the presence of cancer stem cells, and high interstitial fluid pressure in tumors. To tackle these challenges, targeted therapy, specifically targeting HER2 (Human Epidermal Growth Factor Receptor 2) as well as EGFR (Epidermal Growth Factor Receptor), is considered a promising approach in cancer treatment. In recent years, phytocompounds have gained recognition as a potential source of chemopreventive and chemotherapeutic agents in tumor cancer treatment. Phytocompounds are compounds derived from medicinal plants that have the potential to treat and prevent cancer. This study aimed to investigate phytocompounds from <i>Prunus amygdalus var amara</i> seeds as inhibitors against EGFR and HER2 enzymes using in silico methods. In this study, fourteen phytocompounds were isolated from <i>Prunus amygdalus var amara</i> seeds and subjected to molecular docking studies to determine their ability to bind to EGFR and HER2 enzymes. The results showed that diosgenin and monohydroxy spirostanol exhibited binding energies comparable to those of the reference drugs, tak-285, and lapatinib. Furthermore, the drug-likeness and ADMET predictions, performed using the admetSAR 2.0 web-server tool, suggested that diosgenin and monohydroxy spirostanol have similar safety and ADMET properties as the reference drugs. To get deeper insight into the structural steadiness and flexibility of the complexes formed between these compounds and theEGFR and HER2 proteins, molecular dynamics simulations were performed for 100 ns. The results showed that the hit phytocompounds did not significantly affect the stability of the EGFR and HER2 proteins and were able to form stable interactions with the catalytic binding sites of the proteins. Additionally, the MM-PBSA analysis revealed that the binding free energy estimates for diosgenin and monohydroxy spirostanol is comparable to the reference drug, lapatinib. This study provides evidence that diosgenin and monohydroxy spirostanol may have the potential to act as dual suppressors of EGFR and HER2. Additional in vivo and in vitro research are needed to certify these results and assess their efficacy and safety as cancer therapy agents. The experimental data reported and these results are in agreement.https://www.mdpi.com/1424-8247/16/5/704bitter almondEGFRHER2molecular dockingADEMTmolecular dynamic |
| spellingShingle | Mohammed Helmy Faris Shalayel Ghassab M. Al-Mazaideh Abdulkareem A. Alanezi Afaf F. Almuqati Meshal Alotaibi Diosgenin and Monohydroxy Spirostanol from <i>Prunus amygdalus var amara</i> Seeds as Potential Suppressors of EGFR and HER2 Tyrosine Kinases: A Computational Approach Pharmaceuticals bitter almond EGFR HER2 molecular docking ADEMT molecular dynamic |
| title | Diosgenin and Monohydroxy Spirostanol from <i>Prunus amygdalus var amara</i> Seeds as Potential Suppressors of EGFR and HER2 Tyrosine Kinases: A Computational Approach |
| title_full | Diosgenin and Monohydroxy Spirostanol from <i>Prunus amygdalus var amara</i> Seeds as Potential Suppressors of EGFR and HER2 Tyrosine Kinases: A Computational Approach |
| title_fullStr | Diosgenin and Monohydroxy Spirostanol from <i>Prunus amygdalus var amara</i> Seeds as Potential Suppressors of EGFR and HER2 Tyrosine Kinases: A Computational Approach |
| title_full_unstemmed | Diosgenin and Monohydroxy Spirostanol from <i>Prunus amygdalus var amara</i> Seeds as Potential Suppressors of EGFR and HER2 Tyrosine Kinases: A Computational Approach |
| title_short | Diosgenin and Monohydroxy Spirostanol from <i>Prunus amygdalus var amara</i> Seeds as Potential Suppressors of EGFR and HER2 Tyrosine Kinases: A Computational Approach |
| title_sort | diosgenin and monohydroxy spirostanol from i prunus amygdalus var amara i seeds as potential suppressors of egfr and her2 tyrosine kinases a computational approach |
| topic | bitter almond EGFR HER2 molecular docking ADEMT molecular dynamic |
| url | https://www.mdpi.com/1424-8247/16/5/704 |
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