Computer-assisted evaluation of plant-derived β-secretase inhibitors in Alzheimer’s disease

Abstract

Background Alzheimer’s disease (AD) is a progressive neurodegenerative age-related dementia that results in memory loss of elderly people. Many hypotheses have been formally articulated till now to decipher the pathogenesis of this disease. According to the compelling amyloidogenic hypothesis, β-secretase is a key regulatory enzyme in AD development and is therefore considered as one of the major targets for the development of drugs to treat AD. In this study, 40 plant-derived phytocompounds, proven to have β-secretase inhibitory activity in different laboratory experiments, were evaluated using computational approaches in order to identify the best possible β-secretase inhibitor(s). Results Amentoflavone (IFD score: − 7.842 Kcal/mol), Bilobetin (IFD score: − 7.417 Kcal/mol), and Ellagic acid (IFD score: − 6.923 Kcal/mol) showed highest β-secretase inhibitory activities with high binding affinity among all the selected phytocompounds and interacted with key amino acids, i.e., Asp32, Tyr71, and Asp228 in the catalytic site of β-secretase. Moreover, these three molecules exhibited promising results in different drug potential assessment experiments and displayed signs of correlation with significant pharmacological and biological activities. Conclusion Amentoflavone, Biolbetin, and Ellagic acid could be investigated further in developing β-secretase-dependent drug for the effective treatment of AD. However, additional in vivo and in vitro experiments might be required to strengthen the findings of this experiment.

Chemical Composition, Antiaging Activities and Molecular Docking Studies of Essential Oils from Acca sellowiana (Feijoa)

“…β‐ secretase is an ideal molecular target for this purpose. The discovery of a potential β‐ secretase inhibitor would support the anticholinesterase activity in the prevention of AD [50] . The docking results of the previously listed compounds against β‐ secretase binding site are shown in Table 2.…”

“…The discovery of a potential β-secretase inhibitor would support the anticholinesterase activity in the prevention of AD. [50] The docking results of the previously listed compounds against β-secretase binding site are shown in Table 2. The six compounds showed similar docking scores.…”

In-Silico Molecular Docking and Pharmaco-Kinetic Activity Analysis of Potential Inhibitors against SARS-CoV-2 Spike Glycoproteins

“…Larger Gap value suggests the hardness of the drug molecules, which is closely associated with the lower chemical reactivity and high kinetic stability. The smaller Gap value indicates the softness of the drug molecules, which signifies low kinetic stability and high chemical reactivity [60][61][62]. All the drugs in this study exhibit lower (<1.3) HOMO-LUMO GAP, indicating high chemical reactivity of the drugs described in Table 6.…”

“…HOMO-LUMO GAP indicates the measurement of kinetic stability [59,60]. HOMO-LUMO GAP is also closely related to the hardness and softness of the compounds.…”

Neuroprotective Potential of Biflavone Ginkgetin: A Review

“…The authors indicated that the importance of the position of hydroxyl groups in two apigenin molecules for the inhibition of β-secretase and the presence of hydroxyl groups in the C3′ and C8″ position might enhance the inhibitory effects. Ullah et al [ 98 ] reviewed β-secretase inhibitors from plant sources and, among them, ginkgetin was a significant inhibitor with a low IC 50 value. In an in silico study performed by Grewal et al [ 99 ], ginkgetin showed a good binding potential on N-methyl-D-aspartate glutamate receptor (NMDA) and beta secretase-1 (BACE-1), and was suggested as a neuroprotective agent.…”