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Phytochemical identification and in silico elucidation of interactions of bioactive compounds from Citrullus lanatus with androgen receptor towards prostate cancer treatment

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Abstract

Androgen receptor (AR) is known to play a crucial role in the development and progression of prostate cancer, and compounds that inhibit its activity are regarded as promising for the development of drugs to treat the disease. This study aimed to investigate the AR-inhibiting potential of Citrullus lanatus fruit compounds for prostate cancer drug development. Following HPLC identification, the binding energies, molecular interactions, and pharmacological potentials of the compounds against AR were elucidated using in silico techniques such as, molecular docking, induced-fit docking, molecular dynamics simulation, and ADMET prediction. Some of the compounds found to be present in Citrullus lanatus fruit included flavonoids such as proanthocyanin, naringin, flavan 3 ol, flavonones, naringenin, epicatechin, citrulline, and catechin. Naringenin exhibited the highest docking score in the molecular docking analysis, followed by resveratrol, ribalinidine, and epicatechin. These compounds share a common AR binding site with the standard ligand, dihydrotestosterone (DHT). Some of the compounds showed favorable ADMET profiles, while others showed at least one toxicity potential. The induced-fit docking of naringenin with AR yielded a higher docking score than the initial score obtained from standard docking while preserving stable molecular contacts with the interacting amino acids. Consistent hydrogen bond interactions of naringenin with PHE 764, ASN 705, and THR 877 of AR, including a persistent pi-pi stacking contact with PHE 764, were observed from the molecular dynamic simulation. The Citrullus lanatus compounds, particularly naringenin, may therefore be considered for further research towards the development of drugs for prostate cancer therapy.

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The data supporting the findings of this study are available within the main text of this article.

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Authors and Affiliations

  1. Department of Biotechnology, Ebonyi State University, Abakaliki, Ebonyi State, Nigeria

    Miracle Destiny Demian & Lilian N. Ebenyi

  2. National Biotechnology Development Agency, Abuja, Nigeria

    Victor Ikechukwu Amasiorah

  3. Department of Biochemistry, Faculty of Basic Medical Science, College of Health Sciences, University of Jos, Jos, Nigeria

    Titilayo Omolara Johnson

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  1. Miracle Destiny Demian
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  2. Victor Ikechukwu Amasiorah
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  3. Titilayo Omolara Johnson
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  4. Lilian N. Ebenyi
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Contributions

All authors design the work. MDD, VIA and LNE carried out the phytochemical profiling of the fruit extract while TOJ did the in silico analysis. TOJ and MDD interpreted the results and wrote the manuscript. LNE supervised the entire project and write-up. All authors approved the publication of the manuscript.

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Correspondence to Titilayo Omolara Johnson or Lilian N. Ebenyi.

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Demian, M.D., Amasiorah, V.I., Johnson, T.O. et al. Phytochemical identification and in silico elucidation of interactions of bioactive compounds from Citrullus lanatus with androgen receptor towards prostate cancer treatment. In Silico Pharmacol. 12, 27 (2024). https://doi.org/10.1007/s40203-024-00193-5

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