Extrapolation of phenolic compounds as multi-target agents against cancer and inflammation

Abstract

Natural products acquire massive structural and chemical diversity, which cannot be coordinated by any synthetic libraries for small molecules and they are continuing to inspire novel discoveries in health sciences. We have performed the computational calculations for geometry optimization and prediction of electronic and structural properties of some plant phenolic compounds through Gaussian 09 program. Energies of molecular orbitals were computed, to mimic out the stabilities arising from charge delocalization and intramolecular interactions. This process indicated the eventual charge transfer within the molecules. The molecular docking and ADMET properties of these compounds with a novel anticancer (HER2) and anti-inflammatory (COX-2) targets revealed that two molecules were capable of inhibiting both the targets, and could be used as multi target inhibitors. Furthermore, molecular dynamics simulation studies were performed to elucidate the binding mechanism and the comparison of inhibitor’s binding mode with diverse biological activities as anticancer and anti-inflammatory agents. A high-quality association was reported among quantum chemical, ADMET, docking, dynamics and MMGBSA results.

Communicated By Ramaswamy H. Sarma

Keywords:

• Plant phenolics
• DFT
• ADMET
• molecular docking
• MD simulations

Acknowledgements

Authors are thankful to IIT Roorkee and IIIT Allahabad for software’s facilities. NK gratefully acknowledges IIT Indore and BHU for lab facility and Dr Nidhi Goel for her valuable suggestions and fruitful discussions.Naresh Kumar and Saurabh Gupta contributed equally in this research article.

Author contributions

NK, NG designed, and NK, NG, SG, TCY performed the experiments. VP and PKV provide the necessary facilities. All authors reviewed and write the manuscript. NK and SG contributed equally as first author.

Disclosure Statement

The authors declare no conflict of interest.

Additional information

Funding

Authors are thankful to UGC, New Delhi India for financial support as Post-Doctoral fellowship (File No. 201718-PDFSS-2017-18-UTT-17095).