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

Egyptian Journal of Medical Human Genetics

Nafisa Ahmed¹  Abida Nurun Nahar¹  Bishajit Sarkar²  Md. Asad Ullah²  Fatema Tuz Johora²  Tanzina Akter³  Yusha Araf⁴ 

[1] Biotechnology Program, Department of Mathematics and Natural Science, School of Data and Sciences, BRAC University;Department of Biotechnology and Genetic Engineering, Faculty of Biological Sciences, Jahangirnagar University;Department of Genetic Engineering and Biotechnology, Faculty of Biological Sciences, University of Chittagong;Department of Genetic Engineering and Biotechnology, School of Life Sciences, Shahjalal University of Science and Technology;

关键词: Alzheimer’s disease;    Amentoflavone;    Bilobetin;    β-secretase;    Docking;    Ellagic acid;   

DOI  :  10.1186/s43042-021-00150-3

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown