Prospect. & struct. insight, binding plant-deriv. molecule of leea indica; inhibitor bace-1

Alzheimer’s disease is a type of dementia that causes problems with memory, thinking and behavior. Symptoms usually develop slowly and get worse over time, becoming severe enough to interfere with daily tasks. Alzheimer’s disease is considered to be the most common neurological disorder and especially in the elderly population. Numerous studies have shown that the inhibitor BACE1 has direct correlation with Alzheimer’s disease pathology. it has also been observed that the BACE1 inhibitor’s functionality is prone to have a very significant influence on treating AD.

Zahid Hosen et al. from the Molecular Modeling and Drug Design Laboratory, Pharmacology Research Division, Bangladesh Council of Scientific and Industrial Research have set out on their search for a reliable and good plant derivative of BACE1 inhibitors from Leea indica for the purpose of structural analysis using the mechanism of combined molecular docking and molecular dynamics based approaches. By using virtual screening approaches against BACE1, an extensive library of Leea indica plant-derived molecules was compiled and computationally screened for inhibitory action.

Insights into the binding mechanisms of the screened molecules were gained using induced fit docking models and classical molecular dynamics along with steered molecular dynamics simulations. The studies revealed two tri-terpenoids, namely ursolic acid and lupeol to have potential activity relevant to BACE1 inhibition. Lupeol showed better binding free energy in MM/GBSA, MM/PBSA and MM/GBVI approaches. Furthermore, classical and steered dynamics revealed favorable hydrophobic interactions between lupeol and catalytic dyad of BACE1. Therefore, this study revealed lupeol as a potent BACE1 inhibitor from Leea indica molecules. However, ursolic acid showed a series of unfavorable interactions with BACE1. The study provides a new avenue for pharmaceutical researchers looking for plant-derived BACE1 inhibitors for AD therapy.

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