Mechanistic insight of Staphylococcus aureus associated skin cancer in humans by Santalum album derived phytochemicals: an extensive computational and experimental approaches
An excessive amount of multidrug-resistant Staphylococcus aureus is commonly associated with actinic keratosis (AK) and squamous cell carcinoma (SCC) by secreted virulence products that induced the chronic inflammation leading to skin cancer which is regulated by staphylococcal accessory regulator (...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-11-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2023.1273408/full |
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| author | Md. Eram Hosen Sumaiya Jahan Supti Shopnil Akash Md. Ekhtiar Rahman Md Omar Faruqe M. Manirujjaman Uzzal Kumar Acharjee Abdel-Rhman Z. Gaafar Lahcen Ouahmane Baye Sitotaw Mohammed Bourhia Rashed Zaman |
| author_facet | Md. Eram Hosen Sumaiya Jahan Supti Shopnil Akash Md. Ekhtiar Rahman Md Omar Faruqe M. Manirujjaman Uzzal Kumar Acharjee Abdel-Rhman Z. Gaafar Lahcen Ouahmane Baye Sitotaw Mohammed Bourhia Rashed Zaman |
| author_sort | Md. Eram Hosen |
| collection | DOAJ |
| description | An excessive amount of multidrug-resistant Staphylococcus aureus is commonly associated with actinic keratosis (AK) and squamous cell carcinoma (SCC) by secreted virulence products that induced the chronic inflammation leading to skin cancer which is regulated by staphylococcal accessory regulator (SarA). It is worth noting that there is currently no existing published study that reports on the inhibitory activity of phytochemicals derived from Santalum album on the SarA protein through in silico approach. Therefore, our study has been designed to find the potential inhibitors of S. aureus SarA protein from S. album-derived phytochemicals. The molecular docking study was performed targeting the SarA protein of S. aureus, and CID:5280441, CID:162350, and CID: 5281675 compounds showed the highest binding energy with −9.4 kcal/mol, −9.0 kcal/mol, and −8.6 kcal/mol respectively. Further, molecular dynamics simulation revealed that the docked complexes were relatively stable during the 100 ns simulation period whereas the MMPBSA binding free energy proposed that the ligands were sustained with their binding site. All three complexes were found to be similar in distribution with the apoprotein through PCA analysis indicating conformational stability throughout the MD simulation. Moreover, all three compounds’ ADMET profiles revealed positive results, and the AMES test did not show any toxicity whereas the pharmacophore study also indicates a closer match between the pharmacophore model and the compounds. After comprehensive in silico studies we evolved three best compounds, namely, Vitexin, Isovitexin, and Orientin, which were conducted in vitro assay for further confirmation of their inhibitory activity and results exhibited all of these compounds showed strong inhibitory activity against S. aureus. The overall result suggests that these compounds could be used as a natural lead to inhibit the pathogenesis of S. aureus and antibiotic therapy for S. aureus-associated skin cancer in humans as well. |
| first_indexed | 2024-03-10T00:44:38Z |
| format | Article |
| id | doaj.art-efa62f99b917483d8ee35592695f5463 |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-03-10T00:44:38Z |
| publishDate | 2023-11-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Chemistry |
| spelling | doaj.art-efa62f99b917483d8ee35592695f54632023-11-23T15:02:24ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462023-11-011110.3389/fchem.2023.12734081273408Mechanistic insight of Staphylococcus aureus associated skin cancer in humans by Santalum album derived phytochemicals: an extensive computational and experimental approachesMd. Eram Hosen0Sumaiya Jahan Supti1Shopnil Akash2Md. Ekhtiar Rahman3Md Omar Faruqe4M. Manirujjaman5Uzzal Kumar Acharjee6Abdel-Rhman Z. Gaafar7Lahcen Ouahmane8Baye Sitotaw9Mohammed Bourhia10Rashed Zaman11Professor Joarder DNA and Chromosome Research Laboratory, Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi, BangladeshDepartment of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi, BangladeshDepartment of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, BangladeshDepartment of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi, BangladeshDepartment of Computer Science and Engineering, University of Rajshahi, Rajshahi, BangladeshDepartment of Structural and Cellular Biology, Tulane University School of Medicine, New Orleans, LA, United StatesDepartment of Genetics, University of Alabama, Birmingham, AL, United StatesDepartment of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi ArabiaLaboratory of Microbial Biotechnologies, Agrosciences and Environment (BioMAgE), Labeled Research Unit-CNRSTN°4, Cadi Ayyad University, Marrakesh, MoroccoDepartment of Biology, Bahir Dar University, Bahir Dar, Ethiopia0Department of Chemistry and Biochemistry, Faculty of Medicine and Pharmacy, Ibn Zohr University, Laayoune, MoroccoProfessor Joarder DNA and Chromosome Research Laboratory, Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi, BangladeshAn excessive amount of multidrug-resistant Staphylococcus aureus is commonly associated with actinic keratosis (AK) and squamous cell carcinoma (SCC) by secreted virulence products that induced the chronic inflammation leading to skin cancer which is regulated by staphylococcal accessory regulator (SarA). It is worth noting that there is currently no existing published study that reports on the inhibitory activity of phytochemicals derived from Santalum album on the SarA protein through in silico approach. Therefore, our study has been designed to find the potential inhibitors of S. aureus SarA protein from S. album-derived phytochemicals. The molecular docking study was performed targeting the SarA protein of S. aureus, and CID:5280441, CID:162350, and CID: 5281675 compounds showed the highest binding energy with −9.4 kcal/mol, −9.0 kcal/mol, and −8.6 kcal/mol respectively. Further, molecular dynamics simulation revealed that the docked complexes were relatively stable during the 100 ns simulation period whereas the MMPBSA binding free energy proposed that the ligands were sustained with their binding site. All three complexes were found to be similar in distribution with the apoprotein through PCA analysis indicating conformational stability throughout the MD simulation. Moreover, all three compounds’ ADMET profiles revealed positive results, and the AMES test did not show any toxicity whereas the pharmacophore study also indicates a closer match between the pharmacophore model and the compounds. After comprehensive in silico studies we evolved three best compounds, namely, Vitexin, Isovitexin, and Orientin, which were conducted in vitro assay for further confirmation of their inhibitory activity and results exhibited all of these compounds showed strong inhibitory activity against S. aureus. The overall result suggests that these compounds could be used as a natural lead to inhibit the pathogenesis of S. aureus and antibiotic therapy for S. aureus-associated skin cancer in humans as well.https://www.frontiersin.org/articles/10.3389/fchem.2023.1273408/fullskin cancerStaphylococcus aureusstaphylococcal accessory regulator (SarA)Santalum albummolecular dockingmolecular dynamics |
| spellingShingle | Md. Eram Hosen Sumaiya Jahan Supti Shopnil Akash Md. Ekhtiar Rahman Md Omar Faruqe M. Manirujjaman Uzzal Kumar Acharjee Abdel-Rhman Z. Gaafar Lahcen Ouahmane Baye Sitotaw Mohammed Bourhia Rashed Zaman Mechanistic insight of Staphylococcus aureus associated skin cancer in humans by Santalum album derived phytochemicals: an extensive computational and experimental approaches Frontiers in Chemistry skin cancer Staphylococcus aureus staphylococcal accessory regulator (SarA) Santalum album molecular docking molecular dynamics |
| title | Mechanistic insight of Staphylococcus aureus associated skin cancer in humans by Santalum album derived phytochemicals: an extensive computational and experimental approaches |
| title_full | Mechanistic insight of Staphylococcus aureus associated skin cancer in humans by Santalum album derived phytochemicals: an extensive computational and experimental approaches |
| title_fullStr | Mechanistic insight of Staphylococcus aureus associated skin cancer in humans by Santalum album derived phytochemicals: an extensive computational and experimental approaches |
| title_full_unstemmed | Mechanistic insight of Staphylococcus aureus associated skin cancer in humans by Santalum album derived phytochemicals: an extensive computational and experimental approaches |
| title_short | Mechanistic insight of Staphylococcus aureus associated skin cancer in humans by Santalum album derived phytochemicals: an extensive computational and experimental approaches |
| title_sort | mechanistic insight of staphylococcus aureus associated skin cancer in humans by santalum album derived phytochemicals an extensive computational and experimental approaches |
| topic | skin cancer Staphylococcus aureus staphylococcal accessory regulator (SarA) Santalum album molecular docking molecular dynamics |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2023.1273408/full |
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