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Persuasive phytoestrogenic imidazole-based selenium N-heterocyclic carbenes: electronic, structural, and in silico anticancer potential investigations

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Abstract

The cellular antioxidant defense mechanism against reactive oxygen species (ROS) depends on selenium, a vital trace element. Numerous selenium-containing compounds have recently displayed a wide range of biological characteristics that make them intriguing scaffolds in medicinal chemistry. Among the several categories of phytoestrogens, Imidazole-Based Selenium N-heterocyclic carbene Compounds (IM-SeNHC) have drawn the most scientific attention. Several IM-SeNHC compounds were chosen for this theoretical study analysis. The goal of this study was to govern the binding capacity of each of the selected IM-SeNHC that have been identified as inhibitors of the proteins responsible for cancer EGFR, hTrkA, HER2, and cMet (PDB codes: 5GTY, 6PL2, 7JXH, and 3RHK, respectively). DFT and molecular docking investigations were carried out employing in silico software for their virtual screening. Conferring to the docking study, ligand 6 formed hydrogen bonds with protein 7JXH’s active pocket, followed by ligand 8 with protein 3RHK and 5GTY, and ligand 9 with protein 6PL2. Conferring to trends in polarizability and dipole moment, the energy difference values (0.299 eV and 0.277 eV) of IM-SeNHC compounds (3 and 8) show the rise in chemical potential, reactivity, and bioactivity brought on by the most stable structural configurations. Additionally, ADME was investigated to discover the pharmacokinetic characteristics of the targeted moieties. The cardiotoxicity analysis was performed, and confidence percentages accompanying these predictions vary across the dataset, ranging from around 57 to 99.9%, indicating differing levels of certainty in the predictions. This research showed that these ligands have a promising future in cancer therapy medications.

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Acknowledgements

The authors are grateful to King Saud University, Riyadh, Saudi Arabia, for funding the work through the Researchers Supporting Project No. (RSPD2024R852).

Funding

This research was funded by King Saud University, Riyadh, Saudi Arabia, through the Researchers Supporting Project No. (RSPD2024R852).

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Authors and Affiliations

  1. School of Chemistry and Chemical Engineering, Linyi University, Linyi, 276000, China

    Sadaf Mutahir & Muhammad Asim Khan

  2. Department of Chemistry, University of Sialkot, Sialkot, 51300, Pakistan

    Sadaf Mutahir, Muhammad Asim Khan, Iqra Asif & Muhammad Atif Tariq

  3. School of Biochemistry and Biotechnology, University of the Punjab, Lahore, 54590, Pakistan

    Zeeshan Mutahir

  4. Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, 11451, Riyadh, Saudi Arabia

    Abdulrahman A. Almehizia

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  1. Sadaf Mutahir
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Contributions

Conceptualization, S.M. and M.A.K.; methodology, I.A. and M.A.K.; software, , A.A.A. and M.A.T.; formal analysis, M.A.K.; investigation, S.M.; resources, S.M. and AA.A.; writing—original draft preparation, S.M., Z.M. and M.A.K.; writing—review and editing, M.A.K.; supervision, S.M. and M.A.K.; project administration, S.M. and M.A.K. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Sadaf Mutahir or Muhammad Asim Khan.

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Mutahir, S., Khan, M.A., Asif, I. et al. Persuasive phytoestrogenic imidazole-based selenium N-heterocyclic carbenes: electronic, structural, and in silico anticancer potential investigations. Struct Chem (2024). https://doi.org/10.1007/s11224-024-02301-9

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