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New Insight into the Pharmacological Importance of Atropine as the Potential Inhibitor of AKR1B1 via Detailed Computational Investigations: DFTs, ADMET, Molecular Docking, and Molecular Dynamics Studies

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Abstract

The aim of this research is to investigate the quantum geometric properties and chemical reactivity of atropine, a pharmaceutically active tropane alkaloid. Using density functional theory (DFT) computations with the B3LYP/SVP functional theory basis set, the most stable geometry of atropine was determined. Additionally, a variety of energetic molecular parameters were calculated, such as the optimized energy, atomic charges, dipole moment, frontier molecular orbital energies, HOMO–LUMO energy gap, molecular electrostatic potential, chemical reactivity descriptors, and molecular polarizability. To determine atropine’s inhibitory potential, molecular docking was used to analyze ligand interactions within the active pockets of aldo–keto reductase (AKR1B1 and AKR1B10). The results of these studies showed that atropine has greater inhibitory action against AKR1B1 than AKR1B10, which was further validated through molecular dynamic simulations by analyzing root mean square deviation (RMSD) and root mean square fluctuations (RMSF). The results of the molecular docking simulation were supplemented with simulation data, and the ADMET characteristics were also determined to predict the drug likeness of a potential compound. In conclusion, the research suggests that atropine has potential as an inhibitor of AKR1B1 and could be used as a parent compound for the synthesis of more potent leads for the treatment of colon cancer associated with the sudden expression of AKR1B1.

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Data Availability

All data generated or analyzed during this study are included in this article (and its supplementary information file).

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Funding

This study was supported by Taif University Researchers supporting project (number TURSP-2020/38), Taif University, Taif, Saudi Arabia, for research resources.

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, 63100, Pakistan

    Syeda Abida Ejaz, Mubashir Aziz & Aftab Ahmed

  2. Department of Biotechnology, College of Science, Taif University, P.O. Box 11099, Taif, 21944, Saudi Arabia

    Saqer S. Alotaibi & Sarah M. Albogami

  3. Laboratory of Organic Electronics, Department of Science and Technology, Linköping University, 60174, Norrköping, Sweden

    Farhan Siddique

  4. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Bahauddian Zakariya University, Multan, 60800, Pakistan

    Farhan Siddique

  5. Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, 22511, AlBeheira, Egypt

    Gaber El-Saber Batiha

Authors
  1. Syeda Abida Ejaz
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  2. Mubashir Aziz
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  3. Aftab Ahmed
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  4. Saqer S. Alotaibi
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  5. Sarah M. Albogami
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  7. Gaber El-Saber Batiha
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Contributions

S.A.E. and G.S.B. devised and supervised the study plan. S.A.E., S.S.A., M.A., and F.S. carried out the molecular docking investigations and DFTs. The MD simulations were performed by S.A.E and M.A. The manuscript write up was carried out by S.A.E., G.S.B., A.A., and S.M.A. All authors read and approved the manuscript for publication.

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Correspondence to Syeda Abida Ejaz.

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Ejaz, S.A., Aziz, M., Ahmed, A. et al. New Insight into the Pharmacological Importance of Atropine as the Potential Inhibitor of AKR1B1 via Detailed Computational Investigations: DFTs, ADMET, Molecular Docking, and Molecular Dynamics Studies. Appl Biochem Biotechnol 195, 5136–5157 (2023). https://doi.org/10.1007/s12010-023-04411-2

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