Preprint / Version 1

Comparative analysis of Doxycycline and Ayurvedic herbs to target metastatic breast cancer: An in-silico approach

Authors

  • Acharya Balkrishna aPatanjali Herbal Research Department, Patanjali Research Institute, Haridwar, India
  • Ajay Kumar cDepartment of Sanskrit, University of Patanjali, Haridwar, India
  • Swami Ishdev cDepartment of Sanskrit, University of Patanjali, Haridwar, India
  • Okeshwar Okeshwar cDepartment of Sanskrit, University of Patanjali, Haridwar, India
  • Hariom Chaturvedi cDepartment of Sanskrit, University of Patanjali, Haridwar, India
  • Kuldeep Mehra cDepartment of Sanskrit, University of Patanjali, Haridwar, India
  • Hariom Verma bDepartment of Yog Science, University of Patanjali, Haridwar, India
  • Rohan Malik bDepartment of Yog Science, University of Patanjali, Haridwar, India
  • Rashmi Mittal aPatanjali Herbal Research Department, Patanjali Research Institute, Haridwar, India
  • Vedpriya Arya aPatanjali Herbal Research Department, Patanjali Research Institute, Haridwar, India

Keywords:

MMP9, Phytochemicals, Doxycycline, Molecualr docking, MD-Simulation

Abstract

Metastasis of breast cancer cells to distant sites including lungs, liver, lymph node, brain and many more have substantially affected the overall survival outcome and distant metastasis free survival rate amongst the diseased individuals. Several pre-clinical and clinical studies were carried out to determine the potency of vigorous inhibitors but they extensively deteriorated the patient’s quality of life. Hence, there exists an urgent need to explore potent natural remedy to fight against metastatic breast cancer. Methods Ayurvedic medicinal plants documented in literature for their ability to fight against breast cancer was screened and their respective active moieties were evaluated to exert inhibitory effect against MMP9. Drug like efficacy of phytochemicals were determined using Molecular docking, MD Simulation, ADMET and MM-PBSA and were further compared with synthetic analogs i.e. Doxycycline. Results Out of 1000 phytochemicals, 12 exerted highest binding affinity (BA) even more than −9.0 kcal/mol that was significantly higher in comparison to Doxycycline which exhibited BA of −7.3 kcal/mol. In comparison to 37 × 30 × 37 Å, 53 × 45 × 66 Å offered best binding site and the highest BA was exhibited by Viscosalactone at LYS104, ASP185, MET338, LEU39, ASN38. During MD Simulation, Viscosalactone-MMP9 complex remained stable for 20 ns and the kinetic, electrostatic and potential energies were observed to be better than Doxycycline. Furthermore, Viscosalactone obtained from Withania somnifera justified the Lipinski’s Rule of 5. Conclusion Viscosalactone obtained from W. somnifera may act as promising drug candidate to fight against metastatic breast cancer. Keywords: MMP9, Phytochemicals, Doxycycline, Molecualr docking, MD-Simulation

Author Biography

Acharya Balkrishna, aPatanjali Herbal Research Department, Patanjali Research Institute, Haridwar, India

cDepartment of Sanskrit, University of Patanjali, Haridwar, India

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