Natural Anthraquinones as Promising MAPK3 Inhibitors for Complementary Cancer Therapy
Objective. MAPK3 activates several nuclear transcription factors, including c-Jun and c-fos, by phosphorylating its downstream cytoplasmic protein, thereby contributing to cell proliferation and survival. Different carcinomas’ initiation, progression, cancer cell metastasis, and drug resistance have...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
Hindawi Limited
2023-01-01
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| Series: | Journal of Chemistry |
| Online Access: | http://dx.doi.org/10.1155/2023/6683470 |
| _version_ | 1797743378174050304 |
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| author | Samaneh Vaziri-Amjad Massoud Moradi-Najmi Amir Taherkhani |
| author_facet | Samaneh Vaziri-Amjad Massoud Moradi-Najmi Amir Taherkhani |
| author_sort | Samaneh Vaziri-Amjad |
| collection | DOAJ |
| description | Objective. MAPK3 activates several nuclear transcription factors, including c-Jun and c-fos, by phosphorylating its downstream cytoplasmic protein, thereby contributing to cell proliferation and survival. Different carcinomas’ initiation, progression, cancer cell metastasis, and drug resistance have been associated with MAPK3 overexpression. Given the need for new and potent MAPK3 inhibitors, this study aimed to explore the potential of anthraquinones (AQs) as organic compounds capable of inhibiting MAPK3. Methods. Using AutoDock 4.0 software, the binding affinity of 21 AQs to the receptor’s active site was evaluated. AQs were ranked based on their ΔGbinding values to the receptor’s active site, with the highest rankings receiving the most favorable scores. The Discovery Studio Visualizer tool was used to demonstrate the interaction modes between the highest-ranked AQs and the MAPK3 catalytic site. Furthermore, a 100-nanosecond molecular dynamics (MD) computer simulation was performed to assess the stability of the docked pose of the most potent enzyme inhibitor identified in this study. Results. The binding affinity of emodin-8-glucoside, aloe-emodin 8-glucoside, pulmatin, rhodoptilometrin, and hypericin to the receptor’s ATP binding cleft was noteworthy, as the ΔGbinding values were < −10 kcal/mol. In addition, emodin-8-glucoside, aloe-emodin 8-glucoside, and pulmatin were found to have inhibition constant values at the picomolar concentration. According to our computer simulation results, the docked pose of emodin-8-glucoside within the active site of MAPK3 achieved a stable state after 70 ns. In other words, the root mean square deviation (RMSD) graph indicated stability within the 70–100 ns timeframe. Conclusion. Inhibition of MAPK3 by emodin-8-glucoside, aloe-emodin 8-glucoside, pulmatin, rhodoptilometrin, and hypericin may have therapeutic potential in cancer treatment. |
| first_indexed | 2024-03-12T14:54:38Z |
| format | Article |
| id | doaj.art-6743fc59943847a2b39041b49699d77c |
| institution | Directory Open Access Journal |
| issn | 2090-9071 |
| language | English |
| last_indexed | 2024-03-12T14:54:38Z |
| publishDate | 2023-01-01 |
| publisher | Hindawi Limited |
| record_format | Article |
| series | Journal of Chemistry |
| spelling | doaj.art-6743fc59943847a2b39041b49699d77c2023-08-15T00:00:01ZengHindawi LimitedJournal of Chemistry2090-90712023-01-01202310.1155/2023/6683470Natural Anthraquinones as Promising MAPK3 Inhibitors for Complementary Cancer TherapySamaneh Vaziri-Amjad0Massoud Moradi-Najmi1Amir Taherkhani2Department of Oral and Maxillofacial MedicineDepartment of Oral and Maxillofacial MedicineResearch Center for Molecular MedicineObjective. MAPK3 activates several nuclear transcription factors, including c-Jun and c-fos, by phosphorylating its downstream cytoplasmic protein, thereby contributing to cell proliferation and survival. Different carcinomas’ initiation, progression, cancer cell metastasis, and drug resistance have been associated with MAPK3 overexpression. Given the need for new and potent MAPK3 inhibitors, this study aimed to explore the potential of anthraquinones (AQs) as organic compounds capable of inhibiting MAPK3. Methods. Using AutoDock 4.0 software, the binding affinity of 21 AQs to the receptor’s active site was evaluated. AQs were ranked based on their ΔGbinding values to the receptor’s active site, with the highest rankings receiving the most favorable scores. The Discovery Studio Visualizer tool was used to demonstrate the interaction modes between the highest-ranked AQs and the MAPK3 catalytic site. Furthermore, a 100-nanosecond molecular dynamics (MD) computer simulation was performed to assess the stability of the docked pose of the most potent enzyme inhibitor identified in this study. Results. The binding affinity of emodin-8-glucoside, aloe-emodin 8-glucoside, pulmatin, rhodoptilometrin, and hypericin to the receptor’s ATP binding cleft was noteworthy, as the ΔGbinding values were < −10 kcal/mol. In addition, emodin-8-glucoside, aloe-emodin 8-glucoside, and pulmatin were found to have inhibition constant values at the picomolar concentration. According to our computer simulation results, the docked pose of emodin-8-glucoside within the active site of MAPK3 achieved a stable state after 70 ns. In other words, the root mean square deviation (RMSD) graph indicated stability within the 70–100 ns timeframe. Conclusion. Inhibition of MAPK3 by emodin-8-glucoside, aloe-emodin 8-glucoside, pulmatin, rhodoptilometrin, and hypericin may have therapeutic potential in cancer treatment.http://dx.doi.org/10.1155/2023/6683470 |
| spellingShingle | Samaneh Vaziri-Amjad Massoud Moradi-Najmi Amir Taherkhani Natural Anthraquinones as Promising MAPK3 Inhibitors for Complementary Cancer Therapy Journal of Chemistry |
| title | Natural Anthraquinones as Promising MAPK3 Inhibitors for Complementary Cancer Therapy |
| title_full | Natural Anthraquinones as Promising MAPK3 Inhibitors for Complementary Cancer Therapy |
| title_fullStr | Natural Anthraquinones as Promising MAPK3 Inhibitors for Complementary Cancer Therapy |
| title_full_unstemmed | Natural Anthraquinones as Promising MAPK3 Inhibitors for Complementary Cancer Therapy |
| title_short | Natural Anthraquinones as Promising MAPK3 Inhibitors for Complementary Cancer Therapy |
| title_sort | natural anthraquinones as promising mapk3 inhibitors for complementary cancer therapy |
| url | http://dx.doi.org/10.1155/2023/6683470 |
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