Molecular Docking and Simulation Studies of Flavanone and its Derived Compounds on PI3K-AKT Pathway Targeting against Cancer

Abstract

Background: Flavanone compounds and its related derivatives are reported to participating in controlling cell cycle, Angiogenesis, and metastasis. Phosphoinositide 3-kinases is major drug target. Methods: Crystalize structure of Phosphoinositide 3-kinases-Akt complex obtained from Protein Data Bank (PDBID: 3CQW) was selected as receptor protein and binding site has been identified with PDBSum Database. Flavanone and its derivatives were retrieved using freely available existing drug database like Drug Bank, Zinc and PubChem. Modifications of new derivatives was performed by altering the flavanone at Beta ring position this modification would help in maintaining stable structural conformation and retaining better anticancer activity. Retrieved Flavanone derivatives from the drug database were docked against 3CQW Protein with advance docking tool FlexX. MD simulations of best molecule were performed with Desmond package by calculating nonbonding interactions such as electrostatic interaction and hydrogen bond stable and favorable conformations were calculated. Results: These interaction studies would help in identifying new potential drug candidate with the help of computer aided drug designing techniques. Conclusion: Natural chemicals have received a lot of attention because of their vast range of applications in human health and disease prevention without creating any negative side effects. Molecular docking is an essential approach for drug development since it allows for effective screening of potential therapeutics in a short amount of time. We hypothesized in this paper that natural Flavanone and its derivatives may be effective as Akt-1 inhibitors.