In-silico Evaluation of Novel Honokiol Derivatives against Breast Cancer Target Protein LKB1

  • Autores: Shahid I.1, Shoaib M.2, Raza R.3, Jahangir M.4, Abbasi S.5, Riasat A.6, Akbar A.7, Mehnaz S.8
  • Afiliações:
    1. Department of Biotechnology, Faculty of Science and Technology,, University of Central Punjab
    2. Department of Pharmacology, Nishtar Medical University
    3. NUMS Department of Biological Sciences, Faculty of Multidisciplinary Studies,, National University of Medical Sciences
    4. Food and Biotechnology Research Center, Pakistan Council of Scientific and Industrial Research, PCSIR Laboratories Complex
    5. NUMS Department of Biological Sciences, Faculty of Multidisciplinary Studies, National University of Medical Sciences
    6. Department of Biochemistry, Government College University, Faisalabad
    7. Department of Biotechnology, Faculty of Science and Technology, University of Central Punjab
    8. School of Biological Sciences, University of the Punjab, Quaid-e- Azam Campus
  • Edição: Volume 23, Nº 12 (2023)
  • Páginas: 1388-1396
  • Seção: Oncology
  • URL: https://kld-journal.fedlab.ru/1871-5206/article/view/694310
  • DOI: https://doi.org/10.2174/1871520623666230330083630
  • ID: 694310

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Resumo

Background: Breast cancer is characterized by uncontrolled cell growth in the breast tissue and is a leading cause of death globally. Cytotoxic effects and reduced efficacy of currently used therapeutics insist to look for new chemo-preventive strategies against breast cancer. LKB1 gene has recently been categorized as a tumor suppressor gene where its inactivation can cause sporadic carcinomas in various tissues. Mutations in the highly conserved LKB1 catalytic domain lead to the loss of function and subsequently elevated expression of pluripotency factors in breast cancer.

Objectives: The utilization of drug-likeness filters and molecular simulation has helped evaluate the pharmacological activity and binding abilities of selected drug candidates to the target proteins in many cancer studies.

Methods: The current in silico study provides a pharmacoinformatic approach to decipher the potential of novel honokiol derivatives as therapeutic agents against breast cancer. AutoDock Vina was used for molecular docking of the molecules. A 100 nano second (ns) molecular dynamics simulation of the lowest energy posture of 3'-formylhonokiol- LKB1, resulting from docking studies, was carried out using the AMBER 18.

Results: Among the three honokiol derivatives, ligand-protein binding energy of 3' formylhonokiol with LKB1 protein was found to be the highest via molecular docking. Moreover, the stability and compactness inferred for 3'- formylhonokiol with LKB1 are suggestive of 3' formylhonokiol being an effective activator of LKB1 via simulation studies.

Conclusion: It was further established that 3'- formylhonokiol displays an excellent profile of distribution, metabolism, and absorption, indicating it is an anticipated future drug candidate.

Sobre autores

Izzah Shahid

Department of Biotechnology, Faculty of Science and Technology,, University of Central Punjab

Autor responsável pela correspondência
Email: info@benthamscience.net

Muhammad Shoaib

Department of Pharmacology, Nishtar Medical University

Email: info@benthamscience.net

Rabail Raza

NUMS Department of Biological Sciences, Faculty of Multidisciplinary Studies,, National University of Medical Sciences

Email: info@benthamscience.net

Muhammad Jahangir

Food and Biotechnology Research Center, Pakistan Council of Scientific and Industrial Research, PCSIR Laboratories Complex

Email: info@benthamscience.net

Sumra Abbasi

NUMS Department of Biological Sciences, Faculty of Multidisciplinary Studies, National University of Medical Sciences

Email: info@benthamscience.net

Areej Riasat

Department of Biochemistry, Government College University, Faisalabad

Email: info@benthamscience.net

Ansa Akbar

Department of Biotechnology, Faculty of Science and Technology, University of Central Punjab

Email: info@benthamscience.net

Samina Mehnaz

School of Biological Sciences, University of the Punjab, Quaid-e- Azam Campus

Email: info@benthamscience.net

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