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Identification of bioactive compounds from Vaccinium vitis-idaea L. (Lingonberry) as inhibitors for treating KRAS-associated cancer: a computational approach

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Abstract

Lung cancer is the cancer of the lung’s epithelial cells typically characterized by difficulty breathing, chest pain, blood-stained coughs, headache, and weight loss. If left unmanaged, lung cancer can spread to other body parts. While several treatment methods exist for managing lung cancer, exploring natural plant sources for developing therapeutics offers great potential in complementing other treatment approaches. In this study, we evaluated the bioactive compounds in Vaccinium vitis-idaea for treating KRAS-associated lung cancer types. In this study, we concentrated on inhibiting the mutated Kirsten rat sarcoma viral oncogene homolog (KRAS) by targeting an associated protein (Phosphodiesterase 6δ) to which KRAS form complexes. We evaluated bioactive compounds from Lingonberry (Vaccinium vitis-idaea L.), adopting computational approaches such as molecular docking, molecular dynamics simulation, molecular mechanics/generalized Born surface area (MM/GBSA) calculations, and pharmacokinetics analysis. A total of 26 out of 39 bioactive compounds of Vaccinium vitis-idaea L. had a higher binding affinity to the target receptor than an approved drug, Sotorasib. Also, further analyses of all lead/top compounds in this study identified (+)—Catechin (Cianidanol), Arbutin, Resveratrol, and Sinapic acid, to be potential drug candidates that could be pursued. In sum, Arbutin, (+)—Catechin, and Sinapic acid are predicted to be the top compound of Vaccinium vitis-idaea L. because of their pharmacokinetic properties and drug-likeness attributes. Also, their stability to the target receptor makes them a potential drug candidate that could be explored for treating KRAS mutation-associated lung cancer.

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Available upon request.

Abbreviations

KRAS:

Kirsten rat sarcoma viral oncogene homolog

PDE6D:

Phosphodiesterase 6δ

RMSD:

Root mean square deviation

RMSF:

Root mean square fluctuation

MW:

Molecular weight

HBD:

Hydrogen bond donor (HBD)

HBA:

Hydrogen bond acceptor (HBA)

iLOGP:

Lipophilicity (iLOGP)

MR:

Molar refractivity

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Acknowledgements

We appreciate Dotun Olaoye’s helpful input during the manuscript preparation.

Funding

This study received no funding.

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Author notes

  1. Ayooluwa Ilesanmi and Gbenga Dairo: First author.

Authors and Affiliations

  1. Department of Sciences and Mathematics, Mississippi University for Women, Columbus, USA

    Ayooluwa Ilesanmi

  2. Department of Biological Sciences, Western Illinois University, Macomb, IL, USA

    Gbenga Dairo

  3. Department of Chemistry, University of Lagos, Lagos, Nigeria

    Sofela Salimat

  4. Department of Biochemistry, Adekunle Ajasin University, Akungba-Akoko, Nigeria

    Damilola S. Bodun & Toheeb A. Balogun

  5. Department of Chemistry, University of Ilorin, Ilorin, Nigeria

    Bibiire Awoyale

  6. Department of Biological Sciences, University of California, San Diego, La Jolla, USA

    Toheeb A. Balogun

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  1. Ayooluwa Ilesanmi
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Contributions

GD and TAB designed the study. AI, SS, DSB, and BA performed virtual screening and chemical library curation. AI, GD, SS, DSB, and TAB performed molecular docking, pharmacokinetic analysis, molecular dynamics simulation, and post-simulation analysis. AI wrote the first draft. GD and TAB critically revised the manuscript. All authors read and approved the final manuscript.

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Correspondence to Gbenga Dairo or Toheeb A. Balogun.

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Ilesanmi, A., Dairo, G., Salimat, S. et al. Identification of bioactive compounds from Vaccinium vitis-idaea L. (Lingonberry) as inhibitors for treating KRAS-associated cancer: a computational approach. In Silico Pharmacol. 11, 32 (2023). https://doi.org/10.1007/s40203-023-00165-1

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