Flavonoids as promising anticancer agents: an in silico investigation of ADMET, binding affinity by molecular docking and molecular dynamics simulations

Abstract

Cancer is one of the most concerning diseases to humankind. Various treatment strategies are being employed for its treatment, out of which use of natural products is an essential one. Flavonoids have proven to be promising anticancer targets since decades. Also, tubulin is a significant biological target for the development of anticancer agents due to its crucial role in mitosis and abundance throughout the body. In the current study, in silico ADMET parameters of 104 flavonoids were examined, followed by molecular docking with the colchicine binding site of Tubulin protein (PDB; Id 4O2B). The best conformation from each flavonoid subcategory with the best docking score (MolDock score) was further subjected to 100 ns of molecular dynamics to investigate the protein-ligand complex’s stability. Different parameters such as RMSD, RMSF, rGy and SASA were calculated for the six flavonoids using molecular dynamic studies. The top most compound from all the six subcategories of flavonoids elicited best behavior in the colchicine binding site of Tubulin protein. This in silico study employing molecular docking and molecular dynamics simulation provides strong evidence for flavonoids to be excellent anti-tubulin agents for the treatment of cancer.

Communicated by Ramaswamy H. Sarma

Keywords:

• Anticancer
• ADMET and physicochemical properties
• flavonoids
• molecular docking
• molecular dynamics
• multi-drug resistance

Acknowledgements

Authors would like to acknowledge the Indian Council of Medical Research (ICMR), New Delhi, India for awarding Senior Research Fellowship (File No. 45/11/2021-BMS-PHA)

Disclosure statement

Authors declare no conflict of interest.

Author contribution

Conceptualization, Avadh Biharee, Pradeep Kumar, Suresh Thareja, Akhlesh K Jain; Investigation, Avadh Biharee, Kailash Jangid; Methodology, Avadh Biharee, Yogesh Singh, Swanand Kulkarni, Arpita Yadav; Software, Avadh Biharee, Kailash Jangid, Yogesh Singh, Arpita Yadav; Molecular Dynamics Simulation, Kailash Jangid, Yogesh singh, Devesh M Savant; Supervision, Pradeep Kumar, Akhlesh K Jain, Suresh Thareja; Visualization, Avadh Biharee, Suresh Thareja, Akhlesh K Jain; Writing-review & editing, Avadh Biharee, Arpita Yadav, Swanand Kulkarni, Yogesh Singh, Pradeep kumar, Suresh Thareja, Akhlesh K Jain.

Additional information

Funding

This work was supported by Indian Council of Medical Research (ICMR), Govt. of India under the SRF-project File No. 45/11/2021-BMS-PHA.