Identification of Promising Lead Compounds from Capsicum annuum Targeting BACE-1 for Alzheimer’s Disease Therapy: A Molecular Docking Study

Year : 2023 | Volume : 01 | Issue : 01 | Page : 43-52

    Aisiri Vijayasimha

  1. Samiksha Bhor

  1. Student, Department of Bioinformatics, BioNome Private Limited, Karnataka, India
  2. Bioinformatics Associate, Department of Bioinformatics, BioNome Private Limited, Karnataka, India


Background: Alzheimer’s disease (AD) is a neurodegenerative disorder affecting millions of people worldwide. Beta-secretase 1 (BACE-1) is an important therapeutic target for AD treatment. Capsicum annuum (CA) is a commonly consumed plant with potential neuroprotective properties. In this study, we aimed to identify potential lead compounds from CA that can target BACE-1 for AD therapy using molecular docking. Methods: A library of 15 compounds from CA was obtained from PubChem, and their structures were optimized using PyRx-v0.8. BACE-1 protein structure was obtained from the Protein Data Bank (PDB). Docking simulations were performed using PyRx-v0.8, and the results were analyzed using BIOVIA Discovery Studio 2019. Results: Among the studied 15 ligands, the best binding affinity was shown by 6 compounds. Capsaicin, Dihydrocapsaicin, Apigenin, Riboflavin, Quercetin, and Luteolin had a binding affinity of -6.4, -8.4, -8.4, -8.5, and -8.7 kcal/mol respectively. Luteolin had the highest binding score of -8.7 kcal/mol, this indicates its best possible inhibitory action with BACE-1. Conclusion: Our study identified Dihydrocapsaicin, and Capsaicin from CA as promising lead compounds that can target BACE-1 for AD therapy. Further in vitro and in vivo studies are needed to validate their therapeutic potential.

Keywords: Alzheimer’s disease, Capsicum annuum, BACE-1, molecular docking

[This article belongs to International Journal of Genetic Modifications and Recombinations(ijgmr)]

How to cite this article: Aisiri Vijayasimha, Samiksha Bhor Identification of Promising Lead Compounds from Capsicum annuum Targeting BACE-1 for Alzheimer’s Disease Therapy: A Molecular Docking Study ijgmr 2023; 01:43-52
How to cite this URL: Aisiri Vijayasimha, Samiksha Bhor Identification of Promising Lead Compounds from Capsicum annuum Targeting BACE-1 for Alzheimer’s Disease Therapy: A Molecular Docking Study ijgmr 2023 {cited 2023 May 18};01:43-52. Available from:

Browse Figures


  1. GBD 2019 Dementia Forecasting Collaborators. Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the Global Burden of Disease Study 2019. Lancet Public Health [Internet]. 2022;7(2):e105–25. Available from:
  2. Sharma S. Alzheimer’s disease: Causes, treatment & basic science review. IP Int J Compr Adv Pharmacol [Internet]. 2021;6(3):108–16. Available from:


  1. Atri A. Current and future treatments in Alzheimer’s disease. Semin Neurol [Internet]. 2019;39(2):227–40. Available from:
  2. Geerts H, Grossberg GT. Pharmacology of acetylcholinesterase inhibitors and N-methyl-D-aspartate receptors for combination therapy in the treatment of Alzheimer’s disease. J Clin Pharmacol [Internet]. 2006;46(7 Suppl 1):8S-16S. Available from:


  1. Hampel H, Vassar R, De Strooper B, Hardy J, Willem M, Singh N, et al. The β-secretase BACE1 in Alzheimer’s disease. Biol Psychiatry [Internet]. 2021;89(8):745–56. Available from:


  1. Exploring the pathogenesis of Alzheimer’s disease in basal forebrain cholinergic neurons: Converging insights from alternative hypotheses.
  2. Akram M, Nawaz A. Effects of medicinal plants on Alzheimer’s disease and memory deficits. Neural Regen Res [Internet]. 2017;12(4):660–70. Available from:
  3. Thuphairo K, Sornchan P, Suttisansanee U. Bioactive compounds, antioxidant activity and inhibition of key enzymes relevant to Alzheimer’s disease from sweet pepper (Capsicum annuum) extracts. Prev Nutr Food Sci [Internet]. 2019;24(3):327–37. Available from:
  4. Bakrim S, Aboulaghras S, El Menyiy N, El Omari N, Assaggaf H, Lee L-H, et al. Phytochemical compounds and nanoparticles as phytochemical delivery systems for Alzheimer’s disease management. Molecules [Internet]. 2022;27(24):9043. Available from:
  5. IMPPAT: A curated database of Indian Medicinal Plants, Phytochemistry And Therapeutics, Karthikeyan Mohanraj#, Bagavathy Shanmugam Karthikeyan#, R.P. Vivek-Ananth#, R.P. Bharath Chand, S.R. Aparna, P. Mangalapandi and Areejit Samal*, Scientific Reports 8:4329 (2018).
  6. Vassar R, Kandalepas PC. The β-secretase enzyme BACE1 as a therapeutic target for Alzheimer’s disease. Alzheimers Res Ther [Internet]. 2011;3(3):20. Available from:
  7. Jabir NR, Rehman MT, Alsolami K, Shakil S, Zughaibi TA, Alserihi RF, et al. Concatenation of molecular docking and molecular simulation of BACE-1, γ-secretase targeted ligands: in pursuit of Alzheimer’s treatment. Ann Med [Internet]. 2021;53(1):2332–44. Available from:
  8. Nelson PT, Jicha GA, Schmitt FA, Liu H, Davis DG, Mendiondo MS, et al. Clinicopathologic correlations in a large Alzheimer disease center autopsy cohort: neuritic plaques and neurofibrillary tangles “do count” when staging disease severity: Neuritic plaques and neurofibrillary tangles “do count” when staging disease severity. J Neuropathol Exp Neurol [Internet].2007;66(12):1136–46.Availablefrom:
  9. Rodriguez RD, Molina M, Leite RP, Sabadin R, Takada LT, Suemoto CK, et al. P1‐359: Neuropathological findings of an early‐onset dementia case with atypical Alzheimer’s disease: How challenging can the clinical diagnosis of mixed ad be? Alzheimers Dement [Internet]. 2018;14(7S_Part_8):P432–P432. Available from:
  10. Kadry H, Noorani B, Cucullo L. A blood-brain barrier overview on structure, function, impairment, and biomarkers of integrity. Fluids Barriers CNS [Internet]. 2020;17(1):69. Available from:
  11. Piccialli I, Tedeschi V, Caputo L, D’Errico S, Ciccone R, De Feo V, et al. Exploring the therapeutic potential of phytochemicals in Alzheimer’s disease: Focus on polyphenols and monoterpenes. Front Pharmacol [Internet]. 2022;13:876614. Available from:
  12. Marashly ET, Bohlega SA. Riboflavin has neuroprotective potential: Focus on Parkinson’s disease and migraine. Front Neurol [Internet]. 2017;8:333. Available from:
  13. Dihydrocapsaicin Attenuates Blood Brain Barrier and Cerebral Damage in Focal Cerebral Ischemia/Reperfusion via Oxidative Stress and Inflammatory Adchara Janyou1, Piyawadee Wicha1.
  14. Pegorini S, Braida D, Verzoni C, Guerini-Rocco C, Consalez GG, Croci L, et al. Capsaicin exhibits neuroprotective effects in a model of transient global cerebral ischemia in Mongolian gerbils. Br J Pharmacol [Internet]. 2005;144(5):727–35. Available from:

Regular Issue Subscription Original Research
Volume 01
Issue 01
Received April 13, 2023
Accepted May 6, 2023
Published May 18, 2023