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Discovery of Potential Phytochemicals from Carica papaya Targeting BRCA-1 in Breast Cancer Treatment

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Abstract

The BRCA1 and BRCA2 are genes that encode a protein that ensures the integrity of DNA and prevents the unregulated cells from proliferating. Mutations in the sequence of these genes are associated with the birth of inherited breast cancers. The research for possible human breast cancer treatment remains a vital step in the drug development process. In this study, in silico investigations involving a computational method for the discovery of active phytochemicals from Carica papaya against the BRCA-1 gene were carried out. The in silico studies for these phytochemicals datasets as BRCA-1 breast cancer therapeutic agents showed promising results through pharmacokinetics and pharmacodynamics studies. The Carica papaya compounds were found to follow the rule of five and have good bioavailability. The ADMET and drug-likeness screening score of the identified ligands also recognized their potential as a promising drug candidate against BRCA-1 while the DFT also confirm better biological and chemical reactivity of Carica papaya compounds with excellent intra-molecular charge transfer between electron donor and electron acceptor site. The results of the molecular docking provided useful information on possible target-lead interactions, demonstrating that the newly developed leads showed a high affinity for BRCA-1 targets and might be investigated for further research.

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Abbreviations

MMGBSA :

Molecular mechanics/generalized born surface area calculation

ADMET :

Absorption, distribution, metabolism and toxicity

Eg :

Energy band gaps

EHOMO :

Highest occupied molecular orbital energy

ELUMO :

Lowest unoccupied molecular orbital energy

I :

Ionization energy

δ :

Chemical softness

A :

Electron affinity

η :

Chemical hardness

μ :

Chemical potential

χ :

Electronegativity

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Acknowledgements

The authors are grateful to Professor Oyeronke A. Odunola and Dr. Amos O. Abolaji of the Department of Biochemistry, College of Medicine, University of Ibadan, for creating an enabling environment and motivation for the success of this study. We are also grateful to Mr. Akewushola Nurudeen for the proofreading services provided towards the completion of this study.

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Authors and Affiliations

  1. Drosophila Laboratory, Department of Biochemistry, University of Ibadan, Ibadan, Oyo State, Nigeria

    Abdulwasiu Ibrahim

  2. Drosophila Research and Training Centre, Ibadan, Oyo State, Nigeria

    Abdulwasiu Ibrahim

  3. Theoretical and Computational Chemistry Unit, Department of Chemical Sciences, Adekunle Ajasin University, Akungba Akoko, Ondo State, Nigeria

    Nureni Ipinloju & Oluwatoba Emmanuel Oyeneyin

  4. Biology Unit, Department of Biological Sciences, Usmanu Danfodiyo University, Sokoto, Nigeria

    Abdulsamad Omotayo Aiyelabegan

  5. Department of Biochemistry and Molecular Biology, Usmanu Danfodiyo University, Sokoto, Nigeria

    Abdulbaki Adio Alfa-Ibrahim & Suleiman Alhaji Muhammad

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  1. Abdulwasiu Ibrahim
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  2. Nureni Ipinloju
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  3. Abdulsamad Omotayo Aiyelabegan
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  5. Suleiman Alhaji Muhammad
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  6. Oluwatoba Emmanuel Oyeneyin
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Contributions

Conceptualization: A. Ibrahim, and N. Ipinloju. Introduction and methodology: A. Ibrahim, A. O Aiyelabegan, and A.A. Alfa-Ibrahim. Formal analysis: A. Ibrahim., and N. Ipinloju. Data curation: A. Ibrahim, and N. Ipinloju. Writing original draft preparation: A. Ibrahim and N. Ipinloju. Writing review and editing: S. A. Muhammad, A. Ibrahim, N. Ipinloju, A. O Aiyelabegan, A.A. O. E. Oyeneyin and Alfa-Ibrahim. Supervision: S. A. Muhammad and O. E. Oyeneyin. All the authors read and approved the final manuscript.

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Correspondence to Abdulwasiu Ibrahim.

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Ibrahim, A., Ipinloju, N., Aiyelabegan, A.O. et al. Discovery of Potential Phytochemicals from Carica papaya Targeting BRCA-1 in Breast Cancer Treatment. Appl Biochem Biotechnol 195, 7159–7175 (2023). https://doi.org/10.1007/s12010-023-04473-2

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