In Silico Study: Combination of α-Mangostin and Chitosan Conjugated with Trastuzumab against Human Epidermal Growth Factor Receptor 2
Breast cancer is a type of cancer with the highest prevalence worldwide. Almost 10–30% of breast cancer cases are diagnosed as positive for HER2 (human epidermal growth factor receptor 2). The currently available treatment methods still exhibit many shortcomings such as a high incidence of side effe...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-07-01
|
| Series: | Polymers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4360/14/13/2747 |
| _version_ | 1797408334750416896 |
|---|---|
| author | Sandra Megantara Nasrul Wathoni Ahmed Fouad Abdelwahab Mohammed Cecep Suhandi Maryam H. Ishmatullah Melisa F. F. D. Putri |
| author_facet | Sandra Megantara Nasrul Wathoni Ahmed Fouad Abdelwahab Mohammed Cecep Suhandi Maryam H. Ishmatullah Melisa F. F. D. Putri |
| author_sort | Sandra Megantara |
| collection | DOAJ |
| description | Breast cancer is a type of cancer with the highest prevalence worldwide. Almost 10–30% of breast cancer cases are diagnosed as positive for HER2 (human epidermal growth factor receptor 2). The currently available treatment methods still exhibit many shortcomings such as a high incidence of side effects and treatment failure due to resistance. This in silico study aims to simulate α-mangostin and chitosan combination conjugated to trastuzumab formulation against HER2 as an effort to improve breast cancer patient therapy. This molecular docking simulation was done through using PatchDock Server. The materials used including the two-dimensional structure of α-mangostin, chitosan, and sodium tripolyphosphate from the PubChem database; trastuzumab FASTA sequence from the DrugBank database; and HER2 structure obtained from a crystal complex with PDB ID: 1N8Z. The results indicated that the particle of α-mangostin and chitosan combinations interacted mostly with the crystallizable fragment (Fc region) of trastuzumab in the conjugation process. The conjugation of trastuzumab to the particle of a combination of α-mangostin and chitosan resulted in the greatest increase in the binding score of the smallest-sized particles (50 Å) with an increase in the score of 3828 and also gave the most similar mode of interaction with trastuzumab. However, the conjugation of trastuzumab eliminated the similarity of the mode of interaction and increased the value of atomic contact energy. Thus, a cominbation of α-mangostin and chitosan conjugated to a trastuzumab formulation was predicted can increase the effectiveness of breast cancer therapy at a relatively small particle size but with the consequence of decreasing atomic contact energy. |
| first_indexed | 2024-03-09T03:56:58Z |
| format | Article |
| id | doaj.art-d1f7bbc1ab524e02ac68ea15bcc69b28 |
| institution | Directory Open Access Journal |
| issn | 2073-4360 |
| language | English |
| last_indexed | 2024-03-09T03:56:58Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Polymers |
| spelling | doaj.art-d1f7bbc1ab524e02ac68ea15bcc69b282023-12-03T14:19:25ZengMDPI AGPolymers2073-43602022-07-011413274710.3390/polym14132747In Silico Study: Combination of α-Mangostin and Chitosan Conjugated with Trastuzumab against Human Epidermal Growth Factor Receptor 2Sandra Megantara0Nasrul Wathoni1Ahmed Fouad Abdelwahab Mohammed2Cecep Suhandi3Maryam H. Ishmatullah4Melisa F. F. D. Putri5Department of Pharmaceutical Analysis and Medicinal Chemistry, Universitas Padjadjaran, Sumedang 45363, West Java, IndonesiaDepartment of Pharmaceutics and Pharmaceutical Technology, Universitas Padjadjaran, Sumedang 45363, West Java, IndonesiaDepartment of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia 61519, EgyptDepartment of Pharmaceutical Analysis and Medicinal Chemistry, Universitas Padjadjaran, Sumedang 45363, West Java, IndonesiaDepartment of Pharmaceutical Analysis and Medicinal Chemistry, Universitas Padjadjaran, Sumedang 45363, West Java, IndonesiaDepartment of Pharmaceutical Analysis and Medicinal Chemistry, Universitas Padjadjaran, Sumedang 45363, West Java, IndonesiaBreast cancer is a type of cancer with the highest prevalence worldwide. Almost 10–30% of breast cancer cases are diagnosed as positive for HER2 (human epidermal growth factor receptor 2). The currently available treatment methods still exhibit many shortcomings such as a high incidence of side effects and treatment failure due to resistance. This in silico study aims to simulate α-mangostin and chitosan combination conjugated to trastuzumab formulation against HER2 as an effort to improve breast cancer patient therapy. This molecular docking simulation was done through using PatchDock Server. The materials used including the two-dimensional structure of α-mangostin, chitosan, and sodium tripolyphosphate from the PubChem database; trastuzumab FASTA sequence from the DrugBank database; and HER2 structure obtained from a crystal complex with PDB ID: 1N8Z. The results indicated that the particle of α-mangostin and chitosan combinations interacted mostly with the crystallizable fragment (Fc region) of trastuzumab in the conjugation process. The conjugation of trastuzumab to the particle of a combination of α-mangostin and chitosan resulted in the greatest increase in the binding score of the smallest-sized particles (50 Å) with an increase in the score of 3828 and also gave the most similar mode of interaction with trastuzumab. However, the conjugation of trastuzumab eliminated the similarity of the mode of interaction and increased the value of atomic contact energy. Thus, a cominbation of α-mangostin and chitosan conjugated to a trastuzumab formulation was predicted can increase the effectiveness of breast cancer therapy at a relatively small particle size but with the consequence of decreasing atomic contact energy.https://www.mdpi.com/2073-4360/14/13/2747breast cancerα-mangostintrastuzumabHER2in silicoFireDock |
| spellingShingle | Sandra Megantara Nasrul Wathoni Ahmed Fouad Abdelwahab Mohammed Cecep Suhandi Maryam H. Ishmatullah Melisa F. F. D. Putri In Silico Study: Combination of α-Mangostin and Chitosan Conjugated with Trastuzumab against Human Epidermal Growth Factor Receptor 2 Polymers breast cancer α-mangostin trastuzumab HER2 in silico FireDock |
| title | In Silico Study: Combination of α-Mangostin and Chitosan Conjugated with Trastuzumab against Human Epidermal Growth Factor Receptor 2 |
| title_full | In Silico Study: Combination of α-Mangostin and Chitosan Conjugated with Trastuzumab against Human Epidermal Growth Factor Receptor 2 |
| title_fullStr | In Silico Study: Combination of α-Mangostin and Chitosan Conjugated with Trastuzumab against Human Epidermal Growth Factor Receptor 2 |
| title_full_unstemmed | In Silico Study: Combination of α-Mangostin and Chitosan Conjugated with Trastuzumab against Human Epidermal Growth Factor Receptor 2 |
| title_short | In Silico Study: Combination of α-Mangostin and Chitosan Conjugated with Trastuzumab against Human Epidermal Growth Factor Receptor 2 |
| title_sort | in silico study combination of α mangostin and chitosan conjugated with trastuzumab against human epidermal growth factor receptor 2 |
| topic | breast cancer α-mangostin trastuzumab HER2 in silico FireDock |
| url | https://www.mdpi.com/2073-4360/14/13/2747 |
| work_keys_str_mv | AT sandramegantara insilicostudycombinationofamangostinandchitosanconjugatedwithtrastuzumabagainsthumanepidermalgrowthfactorreceptor2 AT nasrulwathoni insilicostudycombinationofamangostinandchitosanconjugatedwithtrastuzumabagainsthumanepidermalgrowthfactorreceptor2 AT ahmedfouadabdelwahabmohammed insilicostudycombinationofamangostinandchitosanconjugatedwithtrastuzumabagainsthumanepidermalgrowthfactorreceptor2 AT cecepsuhandi insilicostudycombinationofamangostinandchitosanconjugatedwithtrastuzumabagainsthumanepidermalgrowthfactorreceptor2 AT maryamhishmatullah insilicostudycombinationofamangostinandchitosanconjugatedwithtrastuzumabagainsthumanepidermalgrowthfactorreceptor2 AT melisaffdputri insilicostudycombinationofamangostinandchitosanconjugatedwithtrastuzumabagainsthumanepidermalgrowthfactorreceptor2 |