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Screening the possible anti-cancer constituents of Hibiscus rosa-sinensis flower to address mammalian target of rapamycin: an in silico molecular docking, HYDE scoring, dynamic studies, and pharmacokinetic prediction

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Abstract

One of the most common malignancies diagnosed and the leading cause of death for cancer-stricken women globally is breast cancer. The molecular subtype affects therapy options because it is a complex disorder with multiple subtypes. By concentrating on receptor activation, mTOR (mammalian target of rapamycin) can be employed as a therapeutic target. The goal of this work was to screen a number of inhibitors produced from Hibiscus rosa-sinensis for possible target to inhibit the mTOR and to determine which has the greatest affinity for the receptor. Primarily, the ionization states of the chosen compounds were predicted using the ChemAxon web platform, and their pKa values were estimated. Given the significance of interactions between proteins in the development of drugs, structure-based virtual screening was done using AutoDock Vina. Approximately 120 Hibiscus components and ten approved anti-cancer drugs, including the mTOR inhibitor everolimus, were used in the comparative analysis. By using Lipinski's rule of five to the chosen compounds, the ADMET profile and drug-likeness characteristics were further examined to assess the anti-breast cancer activity. The compounds with the highest ranked binding poses were loaded using the SeeSAR tool and the HYDE scoring to give interactive, desolvation, and visual ΔG estimation for ligand binding affinity assessment. Following, the prospective candidates underwent three replicas of 100 ns long molecular dynamics simulations, preceded with MM-GBSA binding free energy calculation. The stability of the protein–ligand complex was determined using root mean square deviation (RMSD), root mean square fluctuation (RMSF), and protein–ligand interactions. The results demonstrated that the best mTOR binding affinities were found for stigmastadienol (107), lupeol (66), and taraxasterol acetate (111), which all performed well in comparison to the control compounds. Thus, bioactive compounds isolated from Hibiscus rosa-sinensis could serve as lead molecules for the creation of potent and effective mTOR inhibitors for the breast cancer therapy.

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All data generated during this study are included in supplementary information files.

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Acknowledgements

The researchers appreciate the support and resources provided by Charmo University and Komar University of Science and Technology in completing this study.

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, College of Medicals and Applied Sciences, Charmo University, Peshawa Street, Chamchamal, 46023, Sulaimani, Iraq

    Hezha O. Rasul

  2. Department of Nanoscience and Applied Chemistry, College of Medicals and Applied Sciences, Charmo University, Peshawa Street, Chamchamal, 46023, Sulaimani, Iraq

    Bakhtyar K. Aziz

  3. Department of Medical Laboratory Science, College of Science, Komar University of Science and Technology, Sulaimani, 46001, Sulaimani, Iraq

    Dlzar D. Ghafour

  4. Department of Chemistry, College of Science, University of Sulaimani, Sulaimani, 46001, Sulaimani, Iraq

    Dlzar D. Ghafour

  5. Department of Chemistry, Faculty of Sciences and Arts, Eskisehir Osmangazi University, Eskişehir, 26040, Turkey

    Arif Kivrak

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HOR: Conceptualization, Methodology, Software, Data Curation, and Writing. BKA: Supervision, Software, and Validation. DDG: Writing and Editing, Visualization, and Resources. AK: Validation, Writing, and Editing. All authors reviewed the manuscript.

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Correspondence to Hezha O. Rasul.

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Rasul, H.O., Aziz, B.K., Ghafour, D.D. et al. Screening the possible anti-cancer constituents of Hibiscus rosa-sinensis flower to address mammalian target of rapamycin: an in silico molecular docking, HYDE scoring, dynamic studies, and pharmacokinetic prediction. Mol Divers 27, 2273–2296 (2023). https://doi.org/10.1007/s11030-022-10556-9

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