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In Silico Prospects and Therapeutic Applications of Ouabagenin and Hydroxylated Corticosteroid Analogues in the Treatment of Lung Cancer

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Abstract

Lung cancer is the second most prevalent carcinoma around the world, and about 80% of patients are of non-small cell lung cancer (NS-CLC). Epidermal growth factor receptor (EGFR) is the most expressed protein kinases in lung cancer and hence can be used in target-related anti-cancer therapy. Here, computational approach is used for the exploration of the anti-cancer potential of new steroid derivatives as previously no in vitro data was available for them. Initially, DFT calculations of all compounds were determined to analyze the electronic density of optimized structures. The HOMO and LUMO orbital analysis of all derivatives was analyzed, to investigate the reactivity of compounds. Afterwards, optimized structures were used for molecular docking studies in which all ouabagenin derivatives were docked within the EGFR active site using MOE software. Moreover, anti-cancer potential of selected derivatives was evaluated on the basis of binding interactions with three anti-cancer proteins. The binding scores of these compounds were compared with the FDA-approved drug, i.e., gefitinib. The findings of current study suggested that selected derivatives exhibited significant inhibiting potential of anti-cancer proteins and EGFR. Particularly, compound OD3 is the potent inhibitor of anti-cancer and EGFR protein with the highest binding energies. These novel steroidal derivatives are subjected to in silico analysis for the first time against lung cancer. These compounds possess potential anti-cancerous properties and can be explored further for in vitro and in vivo studies.

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Data Availability

All the relevant data is included in the main manuscript. All other data will be available upon reasonable request.

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Acknowledgements

The authors of this article are very much thankful to the Princess Nourah bint Abdulrahman University, Saudi Arabia, for providing the research support grant (Project/grant no. PNURSP2022R142).

Funding

The Princess Nourah bint Abdulrahman University, Saudi Arabia, provided the research grant (Project/grant no. PNURSP2022R142).

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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 & Muhammad Sajjad Bilal

  2. Tehsil Head Quarter Hospital, Taunsa Sharif, Taunsa, 32100, Pakistan

    Pervez Rashid Birmani

  3. Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh, 11671, Saudi Arabia

    Bshra A. Alsfouk

  4. Department of Physics, College of Science, Princess Nourah Bint Abdulrahman University, P.O. Box 84428, Riyadh, 11671, Saudi Arabia

    F. F. Alharbi

  5. Bahawalpur College of Pharmacy, Bahawalpur Medical and Dental College, Bahawalpur, Pakistan

    Sidra Hassan

  6. Molecular Biology and Bioinformatics Laboratory, Department of Biochemistry, School of Life Sciences, Federal University of Technology, PMB 704, Akure, Ondo State, Nigeria

    Haruna Isiyaku Umar

  7. Department of Physics, Faculty of Science and Humanities, Ed Dawadmi, Shaqra University, Shaqra, Saudi Arabia

    Muawya Elhadi

Authors
  1. Syeda Abida Ejaz
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  2. Mubashir Aziz
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  3. Pervez Rashid Birmani
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  4. Bshra A. Alsfouk
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  5. F. F. Alharbi
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  6. Muhammad Sajjad Bilal
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  7. Sidra Hassan
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  8. Haruna Isiyaku Umar
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  9. Muawya Elhadi
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Contributions

The study plan was designed and supervised by S.A. Ejaz, B.A.A. and F.F. Alharbi. The whole experimental work was carried out by M. Aziz and M.S.B., following the directions of S.A. Ejaz and H.I. Umar. The manuscript writeup was carried out by S. Hassan and P.R.B. under the guidance of S.A. Ejaz. The subject experts A.A and H.O.E authenticate the study concept and help in revision. M.E. and M. Aziz were involved in M.D studies and in revision; they help in correction and proofreading. 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., Birmani, P.R. et al. In Silico Prospects and Therapeutic Applications of Ouabagenin and Hydroxylated Corticosteroid Analogues in the Treatment of Lung Cancer. Appl Biochem Biotechnol 194, 6106–6125 (2022). https://doi.org/10.1007/s12010-022-04083-4

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