Mechanistic insight of Staphylococcus aureus associated skin cancer in humans by Santalum album derived phytochemicals: an extensive computational and experimental approaches

• Published in: Frontiers in chemistry Vol. 11; p. 1273408
• Main Authors: Hosen, Md Eram, Jahan Supti, Sumaiya, Akash, Shopnil, Rahman, Md Ekhtiar, Faruqe, Md Omar, Manirujjaman, M, Acharjee, Uzzal Kumar, Gaafar, Abdel-Rhman Z, Ouahmane, Lahcen, Sitotaw, Baye, Bourhia, Mohammed, Zaman, Rashed
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 2023
• Subjects: molecular docking; molecular dynamics; Santalum album; skin cancer; staphylococcal accessory regulator (SarA); Staphylococcus aureus; antibacterial activity; skin cancer; molecular docking; staphylococcal accessory regulator (SarA); ADMET prediction; molecular dynamics; Santalum album; Staphylococcus aureus
• ISSN: 2296-2646; 2296-2646
• DOI: 10.3389/fchem.2023.1273408

An excessive amount of multidrug-resistant
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
on the SarA protein through
approach. Therefore, our study has been designed to find the potential inhibitors of
s SarA protein from
-derived phytochemicals. The molecular docking study was performed targeting the SarA protein of
, 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
studies we evolved three best compounds, namely, Vitexin, Isovitexin, and Orientin, which were conducted
assay for further confirmation of their inhibitory activity and results exhibited all of these compounds showed strong inhibitory activity against
The overall result suggests that these compounds could be used as a natural lead to inhibit the pathogenesis of
and antibiotic therapy for
-associated skin cancer in humans as well.