Screening, docking, and molecular dynamics analysis of Mitragyna speciosa (Korth.) compounds for targeting HER2 in breast cancer
Breast cancer remains the most commonly diagnosed cancer among women worldwide, with approximately 2.3 million new cases reported in 2022. In the United States alone, an estimated 310,720 new cases of female breast cancer are expected in 2024. HER2-positive breast cancer, characterized by the overex...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-12-01
|
| Series: | Current Research in Structural Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2665928X2500008X |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849473427206832128 |
|---|---|
| author | Nabila Hadiah Akbar Farendina Suarantika Taufik Muhammad Fakih Ariranur Haniffadli Khoirunnisa Muslimawati Aditya Maulana Perdana Putra |
| author_facet | Nabila Hadiah Akbar Farendina Suarantika Taufik Muhammad Fakih Ariranur Haniffadli Khoirunnisa Muslimawati Aditya Maulana Perdana Putra |
| author_sort | Nabila Hadiah Akbar |
| collection | DOAJ |
| description | Breast cancer remains the most commonly diagnosed cancer among women worldwide, with approximately 2.3 million new cases reported in 2022. In the United States alone, an estimated 310,720 new cases of female breast cancer are expected in 2024. HER2-positive breast cancer, characterized by the overexpression of the human epidermal growth factor receptor 2 (HER2), accounts for about 20 % of all breast cancer cases. The development of anti-HER2 therapies has significantly improved survival rates for patients with HER2-positive breast cancer. In this study, we employed in silico methods to evaluate the potential of natural alkaloids, Mitragynine and 7-Hydroxymitragynine, as HER2 inhibitors. Molecular docking revealed binding energies of −7.56 kcal/mol and −8.77 kcal/mol, respectively, with key interactions involving residues such as Leu726, Val734, Ala751, Lys753, Thr798, and Asp863. Molecular dynamics simulations demonstrated the stability of all three complexes, including Mitragynine, 7-Hydroxymitragynine, and Native (SYR127063), over the simulation period. Mitragynine exhibited stronger interaction stability, supported by a higher hydrogen bond occupancy of 39.19 %, compared to 4.32 % for 7-Hydroxymitragynine, while Native (SYR127063) displayed the highest occupancy at 49.66 %. MM-PBSA analysis further validated these findings, with Native (SYR127063) exhibiting the most favorable total binding energy of −163.448 ± 17.288 kJ/mol, followed by Mitragynine at −112.33 ± 22.41 kJ/mol, and 7-Hydroxymitragynine at −103.56 ± 15.61 kJ/mol. ADMET, physicochemical properties, and drug-likeness evaluations indicated that all compounds satisfy Lipinski, Ghose, Veber, Egan, and Muegge rules, confirming their suitability as lead-like molecules. Based on these findings, Mitragynine and 7-Hydroxymitragynine are promising candidates for HER2-targeted breast cancer therapy, with further experimental validation recommended to confirm their clinical potential. |
| format | Article |
| id | doaj-art-d5c857814a984e11b28a4d902c922b13 |
| institution | Kabale University |
| issn | 2665-928X |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Current Research in Structural Biology |
| spelling | doaj-art-d5c857814a984e11b28a4d902c922b132025-08-20T03:24:08ZengElsevierCurrent Research in Structural Biology2665-928X2025-12-011010017110.1016/j.crstbi.2025.100171Screening, docking, and molecular dynamics analysis of Mitragyna speciosa (Korth.) compounds for targeting HER2 in breast cancerNabila Hadiah Akbar0Farendina Suarantika1Taufik Muhammad Fakih2Ariranur Haniffadli3Khoirunnisa Muslimawati4Aditya Maulana Perdana Putra5Pharmacist Professional Education Study Program (PPSP), Faculty of Mathematics and Natural Sciences, Universitas Lambung Mangkurat, Jl. Brig Jend. Hasan Basri, Banjarmasin, South Kalimantan, 70123, Indonesia; Corresponding author.Pharmacist Professional Education Study Program (PPSP), Faculty of Mathematics and Natural Sciences, Universitas Islam Bandung, Jl. Batik Halus, Bandung, West Java, 40123, IndonesiaDepartment of Pharmacy, Faculty of Mathematics and Natural Sciences, Universitas Islam Bandung, Jl. Ranggagading, Bandung, West Java, 40116, IndonesiaKorean Medicine Convergence Science Major of KIOM School, University of Science and Technology (UST), Daejeon, 34113, Republic of Korea; Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine (KIOM), 111 Geonjaero, Naju-si, Jollanam-do, 58245, Republic of KoreaPharmacist Professional Education Study Program (PPSP), Faculty of Mathematics and Natural Sciences, Universitas Lambung Mangkurat, Jl. Brig Jend. Hasan Basri, Banjarmasin, South Kalimantan, 70123, IndonesiaDepartment of Pharmacy, Faculty of Mathematics and Natural Sciences, Universitas Lambung Mangkurat, Jl. Brig Jend. Hasan Basri, Banjarmasin, South Kalimantan, 70123, IndonesiaBreast cancer remains the most commonly diagnosed cancer among women worldwide, with approximately 2.3 million new cases reported in 2022. In the United States alone, an estimated 310,720 new cases of female breast cancer are expected in 2024. HER2-positive breast cancer, characterized by the overexpression of the human epidermal growth factor receptor 2 (HER2), accounts for about 20 % of all breast cancer cases. The development of anti-HER2 therapies has significantly improved survival rates for patients with HER2-positive breast cancer. In this study, we employed in silico methods to evaluate the potential of natural alkaloids, Mitragynine and 7-Hydroxymitragynine, as HER2 inhibitors. Molecular docking revealed binding energies of −7.56 kcal/mol and −8.77 kcal/mol, respectively, with key interactions involving residues such as Leu726, Val734, Ala751, Lys753, Thr798, and Asp863. Molecular dynamics simulations demonstrated the stability of all three complexes, including Mitragynine, 7-Hydroxymitragynine, and Native (SYR127063), over the simulation period. Mitragynine exhibited stronger interaction stability, supported by a higher hydrogen bond occupancy of 39.19 %, compared to 4.32 % for 7-Hydroxymitragynine, while Native (SYR127063) displayed the highest occupancy at 49.66 %. MM-PBSA analysis further validated these findings, with Native (SYR127063) exhibiting the most favorable total binding energy of −163.448 ± 17.288 kJ/mol, followed by Mitragynine at −112.33 ± 22.41 kJ/mol, and 7-Hydroxymitragynine at −103.56 ± 15.61 kJ/mol. ADMET, physicochemical properties, and drug-likeness evaluations indicated that all compounds satisfy Lipinski, Ghose, Veber, Egan, and Muegge rules, confirming their suitability as lead-like molecules. Based on these findings, Mitragynine and 7-Hydroxymitragynine are promising candidates for HER2-targeted breast cancer therapy, with further experimental validation recommended to confirm their clinical potential.http://www.sciencedirect.com/science/article/pii/S2665928X2500008XBreast cancer (BC)Human epidermal growth factor receptor 2 (HER2)Mitragyna speciosa (Korth.)Natural compounds screeningMolecular interactions approach |
| spellingShingle | Nabila Hadiah Akbar Farendina Suarantika Taufik Muhammad Fakih Ariranur Haniffadli Khoirunnisa Muslimawati Aditya Maulana Perdana Putra Screening, docking, and molecular dynamics analysis of Mitragyna speciosa (Korth.) compounds for targeting HER2 in breast cancer Current Research in Structural Biology Breast cancer (BC) Human epidermal growth factor receptor 2 (HER2) Mitragyna speciosa (Korth.) Natural compounds screening Molecular interactions approach |
| title | Screening, docking, and molecular dynamics analysis of Mitragyna speciosa (Korth.) compounds for targeting HER2 in breast cancer |
| title_full | Screening, docking, and molecular dynamics analysis of Mitragyna speciosa (Korth.) compounds for targeting HER2 in breast cancer |
| title_fullStr | Screening, docking, and molecular dynamics analysis of Mitragyna speciosa (Korth.) compounds for targeting HER2 in breast cancer |
| title_full_unstemmed | Screening, docking, and molecular dynamics analysis of Mitragyna speciosa (Korth.) compounds for targeting HER2 in breast cancer |
| title_short | Screening, docking, and molecular dynamics analysis of Mitragyna speciosa (Korth.) compounds for targeting HER2 in breast cancer |
| title_sort | screening docking and molecular dynamics analysis of mitragyna speciosa korth compounds for targeting her2 in breast cancer |
| topic | Breast cancer (BC) Human epidermal growth factor receptor 2 (HER2) Mitragyna speciosa (Korth.) Natural compounds screening Molecular interactions approach |
| url | http://www.sciencedirect.com/science/article/pii/S2665928X2500008X |
| work_keys_str_mv | AT nabilahadiahakbar screeningdockingandmoleculardynamicsanalysisofmitragynaspeciosakorthcompoundsfortargetingher2inbreastcancer AT farendinasuarantika screeningdockingandmoleculardynamicsanalysisofmitragynaspeciosakorthcompoundsfortargetingher2inbreastcancer AT taufikmuhammadfakih screeningdockingandmoleculardynamicsanalysisofmitragynaspeciosakorthcompoundsfortargetingher2inbreastcancer AT ariranurhaniffadli screeningdockingandmoleculardynamicsanalysisofmitragynaspeciosakorthcompoundsfortargetingher2inbreastcancer AT khoirunnisamuslimawati screeningdockingandmoleculardynamicsanalysisofmitragynaspeciosakorthcompoundsfortargetingher2inbreastcancer AT adityamaulanaperdanaputra screeningdockingandmoleculardynamicsanalysisofmitragynaspeciosakorthcompoundsfortargetingher2inbreastcancer |