In-vitro enzyme inhibition, kinetics, molecular docking and dynamics simulation approaches to decoding the mechanism of Ficus virens in cholinesterase inhibition

Abstract

In the current study, we investigate the bioactive potentials and mode of action of Ficus virens bark (FVB) extract against cholinesterase enzymes, via in-vitro cell-free cholinesterase inhibition kinetics, molecular docking, ADMET and dynamic simulation. Our results illustrated that FVBM extract showed better DPPH-free radical scavenging activity (IC50 = 17.8 ± 0.46 µg/ml) and AChE inhibitory ability (IC50 = 37.2 ± 0.43 µg/ml). Kinetics study explored the mixed inhibition of AChE enzyme by FVBM extract. Furthermore, molecular docking demonstrates that compounds Diethyl Phthalate and Dinopol NOP present in FVBM extract have good ΔG: −8.6 kcal/mol and Ki; 2.01 × 106 M−1 for AChE enzyme than BuChE enzyme (ΔG: −7.6 and Ki: 3.72 × 105 M−1). A simulation study of 200 ns of best two hits and Tacrine confirms that these compounds remained inside the binding pocket of proteins and formed a stable protein-ligand complex via interacting with key residue. Further studies could provide a better understanding of the therapeutic potential of these promising compounds.