Molecular modeling study of the inhibition effect of a group of Alkaloids on AchE enzyme to treat Alzheimer’s disease
DOI:
https://doi.org/10.5281/zenodo.20117609Keywords:
Molecular modeling, Alzheimer's Disease, Acetylcholine Esterase Ache, Huperzine A, AlkaloidsAbstract
Objective: Procedure a molecular modeling study on a group of Alkaloids that have an inhibition effect on AchE enzyme in the brain of Alzheimer’ s patient.
Materials and Methods: molecular modeling was done by iGemdock software using the standard and accurate docking. It required downloading the structure of the target enzyme AchE which found in the brain of Alzheimer patient from the Protein Data Bank and then the chemical compound formuls for 101 alkaloids compound were collected from the Pubchem. The formulas were drawn with the Chemdraw program, and the docking process was completed between the target enzyme AchE and the studied compounds.In addition, applied Lapinski and Weber’s rules to the group of studied compounds in order to predict the bioavailability of these compounds. Data for these two rules were collected from the pubchem website.
Results: the results showed that 20 compounds achieved binding energy higher than the standard compound Huperzine A. These results indicate that it can be suggested as AchE inhibitors in treatment plans for Alzheimer’s patient
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References
[1] T. I. Adelusi et al., “Molecular modeling in drug discovery,” Informatics in Medicine Unlocked, vol. 29, Art. no. 100880, 2022, doi: 10.1016/j.imu.2022.100880.
[2] M. J. Friedli and N. C. Inestrosa, “Huperzine A and its neuroprotective molecular signaling in Alzheimer's disease,” Molecules, vol. 26, no. 21, Art. no. 6531, 2021, doi: 10.3390/molecules26216531.
[3] K. Hsu, Y. Chen, S. Lin, and J. Yang, “iGEMDOCK: A graphical environment of enhancing GEMDOCK using pharmacological interactions and post-screening analysis,” BMC Bioinformatics, vol. 12, suppl. 1, Art. no. S33, 2011, doi: 10.1186/1471-2105-12-S1-S33.
[4] Y. Jia et al., “Oxymatrine ameliorates agomelatine-induced hepatocyte injury through promoting proteasome-mediated CHOP degradation,” Biomedicine & Pharmacotherapy, vol. 114, Art. no. 108784, 2019, doi: 10.1016/j.biopha.2019.108784.
[5] A. E. Lohning, S. M. Levonis, B. Williams-Noonan, and S. S. Schweiker, “A practical guide to molecular docking and homology modelling for medicinal chemists,” Current Topics in Medicinal Chemistry, vol. 17, no. 18, 2017, doi: 10.2174/1568026617666170130110827.
[6] S. F. McHardy, H. L. Wang, S. V. McCowen, and M. C. Valdez, “Recent advances in acetylcholinesterase inhibitors and reactivators: An update on the patent literature (2012–2015),” Expert Opinion on Therapeutic Patents, vol. 27, no. 4, pp. 455–476, 2017, doi: 10.1080/13543776.2017.1272571.
[7] H. S. Nhan, K. Chiang, and E. H. Koo, “The multifaceted nature of amyloid precursor protein and its proteolytic fragments: Friends and foes,” Acta Neuropathologica, vol. 129, no. 1, pp. 1–19, 2014, doi: 10.1007/s00401-014-1347-z.
[8] M. Ratia et al., “Huprine X and Huperzine A improve cognition and regulate some neurochemical processes related with Alzheimer's disease in triple transgenic mice (3xTg-AD),” Neurodegenerative Diseases, vol. 11, no. 3, pp. 129–140, 2012, doi: 10.1159/000336427.
[9] H. Salim, T. Mourad, R. Al-kurdi, D. almirand R. Al-Saleh, “Studying the effect of some compounds found in some essential oils on the penicillin-binding protein in Staphylococcus aureus, using molecular docking”, Journal of Al-Wataniya Private University, vol. 1, no. 1, pp. 214–224, Dec. 2023, doi: 10.5281/zenodo.19351711.
[10] H. salim, T. Mourad, R. Al Trkmanyand L. Arroub, “Molecular modeling study of the effect of a group of compounds extracted from some essential oils on the KAS I enzyme in tuberculosis bacteria”, Journal of Al-Wataniya Private University, vol. 2, no. 1, pp. 117–128, Jun. 2024, doi: 10.5281/zenodo.20252507.
[11] A. Stepezynska et al., “Staurosporine and conventional anticancer drugs induce overlapping, yet distinct pathways of apoptosis and caspase activation,” Oncogene, vol. 20, no. 10, pp. 1193–1202, 2001, doi: 10.1038/sj.onc.1204221.
[12] L. D. S. Tascone and C. M. De Campos Bottino, “Neurobiology of neuropsychiatric symptoms in Alzheimer's disease: A critical review with a focus on neuroimaging,” Dementia & Neuropsychologia, vol. 7, no. 3, pp. 236–243, 2013, doi: 10.1590/S1980-57642013DN70300002.
[13] M. Teodoro and L. Kavraki, “Conformational flexibility models for the receptor in structure-based drug design,” Current Pharmaceutical Design, vol. 9, no. 20, pp. 1635–1648, 2003, doi: 10.2174/1381612033454595.
[14] C. Van Cauwenberghe, C. Van Broeckhoven, and K. Sleegers, “The genetic landscape of Alzheimer disease: Clinical implications and perspectives,” Genetics in Medicine, vol. 18, no. 5, pp. 421–430, 2015, doi: 10.1038/gim.2015.117.
[15] J. Zhen, Y. Dai, T. Villani, D. Giurleo, J. Simon, and Q. Wu, “Synthesis of novel flavonoid alkaloids as α-glucosidase inhibitors.”
[16] X. Zhao, D. Wu, X. Ma, J. Wang, W. Hou, and W. Zhang, “Exosomes as drug carriers for cancer therapy and challenges regarding exosome uptake,” Biomedicine & Pharmacotherapy, vol. 128, Art. no. 110237, 2020, doi: 10.1016/j.biopha.2020.110237.
[17] M. Zhong et al., “Rhynchophylline alleviates cognitive deficits in multiple transgenic mouse models of Alzheimer's disease via modulating neuropathology and gut microbiota,” Acta Pharmacologica Sinica, 2025.
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