Kinetics and computational study of butyrylcholinesterase inhibition by methylrosmarinate: relevance to Alzheimer’s disease treatment

Butyrylcholinesterase (BChE) performs a significant function in Alzheimer’s disease progression. Experimental studies have shown that the function of BChE in the attenuation of cholinergic neurotransmission is essentially altered in brains of advanced AD patients. Here, using the complimentary methods of enzyme kinetic studies, molecular modeling and protein-ligand interaction profiling, we sought to reveal the mechanistic and structural features of BChE-methyrosmarinate interactions. Molecular docking simulations revealed that methylrosmarinate dwelled well in the active centre of BChE, where it got involved in stabilizing non-covalent associations with myriad subsites. Enzyme kinetic experiments showed that the Vm and Ks values were 156.20 ± 3.11 U mg−1 protein and 0.13 ± 0.01 μM, respectively. The inhibition studies showed that methylrosmarinate apparently inhibited BChE in a linear mixed manner, with an IC50 value of 10.31 μM and a Ki value of 3.73 ± 1.52 μM. Taken together, the extremely reduced Ki value and the increased number of BChE–methylrosmarinate interactions presuppose that methylrosmarinate is a good inhibitor of BChE, despite the fact that the mechanism for the effect of BChE inhibition on several pathological conditions in vivo remains unexplored.