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Study of Glabranin as an Inhibitor Against Prostate Cancer: Molecular Docking, Molecular Dynamics Simulation, MM-PBSA Calculation and QSAR Prediction

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Abstract

Prostate cancer is the World's second most frequent malignancy, with the fifth-highest male mortality rate. In advanced prostate cancer patients, point mutations such as T877A and W741L are prevalent, imparting treatment resistance and hence promoting cancer development. The emergence of drug resistance in prostate cancer necessitates the development of suitable ligands to allow for stronger interactions with the receptors, which can inhibit cancer progression. The present study focuses on flavonoids produced by plants, which may act as inhibitors of point mutations like T877A and W741L in prostate cancer. This research was conducted using an in-silico method where the compound Glabranin and its derivatives were virtually screened to identify potential drugs for combating such point mutations. Thirty-five Molecular Dockings were performed to find the ligand-receptor complexes with the lowest binding energy. Moreover, employing a variety of tools, ligands were evaluated for drug-likeness and toxicity, indicating a promising drug candidate. Based on the results of Molecular Docking, Drug-likeness, and ADMET testing, eight structures were subjected to a 100 ns Molecular Dynamics simulation. A QSAR analysis was also performed based on the simulation findings. In this study, it was revealed that GlaMod2 phytocompound was effective against T877A and W741L mutations in prostate cancer. It was observed that the phytocompound was stable and had potential properties for the development of a novel drug to combat prostate cancer and drug resistance This phytocompound may therefore be effective in the development of prostate cancer inhibitors for patients with mutant androgen receptors.

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Acknowledgements

We acknowledge the Bioinformatics Infrastructure Facility, C.V.Sc., Khanapara, Guwahati, sponsored by the Department of Biotechnology, Ministry of Science and Technology, Govt. of India for providing facilities to conduct molecular dynamics studies in a high-performance Dell Precision Tesla 5600 workstation with 12 CPUs and 1 NVIDIA Tesla C2075 graphics processing unit (GPU). We would also like to thank the Vice Chancellor, Assam Don Bosco University for providing the research facilities. The authors appreciate the continuous encouragement and advice from the Director, School of Life Science, Assam Don Bosco University.

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The authors declare that no funding was received to assist with the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Biochemistry, Assam Don Bosco University, Guwahati, India

    Rene Barbie Browne

  2. BIF Centre, Department of Animal Biotechnology, College of Veterinary Science, Assam Agricultural University, Guwahati, India

    Nabajyoti Goswami

  3. Department of Animal Biotechnology, College of Veterinary Science, Assam Agricultural University, Guwahati, India

    Probodh Borah

  4. Department of Bio-Sciences, Assam Don Bosco University, Guwahati, 782402, India

    Jayanti Datta Roy

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  1. Rene Barbie Browne
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  2. Nabajyoti Goswami
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Contributions

The manuscript was written through the contributions of all authors. All authors have approved the final version of the manuscript. R. B. B. has designed and compiled the Manuscript. J. D. R. has conceived and supervised the research. N. G. has guided the computational work and also in performing the Molecular Dynamics Simulation studies. P. B. who is the Coordinator, BIF, and Head of the Department of Animal Biotechnology, College of Veterinary Science has guided and allowed to perform molecular dynamics simulation studies in a high-performance workstation in his lab. All these above-mentioned authors contributed equally to the successful completion of the research work.

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Browne, R.B., Goswami, N., Borah, P. et al. Study of Glabranin as an Inhibitor Against Prostate Cancer: Molecular Docking, Molecular Dynamics Simulation, MM-PBSA Calculation and QSAR Prediction. Ind J Clin Biochem (2023). https://doi.org/10.1007/s12291-023-01134-3

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