Aim: Aberrant activity of class I histone deacetylases (HDACs) has strong implications for various cancers. Targeting these HDACs with synthetic HDAC inhibitors has shown significant side effects such as atrial fibrillation and QT prolongation emphasizing the need of natural inhibitors as substitutes to synthetic ones.
Results: The binding propensity of the two plant-derived inhibitors apigenin and luteolin towards class I HDAC isoforms was checked using extra-precision molecular docking and implicit solvation MMGBSA. Apigenin showed a superior binding affinity against these isoforms as compared to luteolin. Both inhibitors docked stable to the binding pocket of these HDACs as determined by molecular dynamics simulation study.
Conclusion: Apigenin and luteolin may serve as substitutes to synthetic inhibitors for effective HDAC based anticancer therapy.
Keywords: HDACi; HDACs; apigenin; energetically optimized structure-based pharmacophores; givinostat; luteolin; molecular docking; molecular dynamics simulation; molecular mechanics-generalized born surface area.