Rational Design of Dual Inhibitors for Alzheimer's Disease: Insights from
Computational Screening of BACE1 and GSK-3β

Magham      Sai Varshini; Ramakkamma      Aishwarya Reddy; Praveen      Thaggikuppe Krishnamurthy; Divakar      Selvaraj

doi:10.2174/0115734099270256231018072007

Abstract

Background: Alzheimer's disease (AD) is one of the most concerned neurodegenerative disorders across the world characterized by amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs), leading to cognitive decline and memory loss. Targeting key pathways involved in AD like Aβ and NFT pathways, are crucial for the development of effective therapeutic strategies. In this study, we aimed to identify and establish promising dual inhibitors targeting BACE1 and GSK-3β, two proteins implicated in Aβ and NFT formation respectively.

Methods: We have used molecular docking, ADME property analysis, and MMGBSA calculations for the identification of hit molecules and further evaluation of binding affinity, drug-like properties, and stability against BACE1 and GSK-3β.

Results: Our results demonstrated strong binding affinities of ZINC000034853956 towards the active sites of both proteins, with favorable interactions involving key residues crucial for inhibitory activity. Additionally, ZINC000034853956 exhibited favorable drug-like properties. MD simulations revealed the stable binding of ZINC000034853956 to both BACE1 and GSK-3β over a 50 ns period, with consistent ligand-protein interactions, such as hydrogen bonding and hydrophobic contacts. These findings highlight the potential of ZINC000034853956 as a promising candidate for AD treatment, acting as a dual inhibitor targeting both BACE1 and GSK-3β. Overall, our study provides valuable insights into the potential of ZINC000034853956 as a dual inhibitor for AD. The strong binding affinity, favorable drug-like properties, and stability observed in MD simulations support its suitability for further optimization and preclinical studies.

Conclusion: Further investigations are warranted to elucidate the precise molecular mechanisms and therapeutic benefits of ZINC000034853956. Our findings offer hope for the development of novel therapeutic interventions targeting crucial pathways involved in AD neurodegeneration.

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Graphical Abstract

[1]
Javaid, S.F.; Giebel, C.; Khan, M.A.B.; Hashim, M.J. Epidemiology of Alzheimer’s disease and other dementias: Rising global burden and forecasted trends. F1000 Res.,  2021, 10, 425.
 [http://dx.doi.org/10.12688/f1000research.50786.1]

[2]
2022 Alzheimer’s disease facts and figures. Alzheimers Dement.,  2022, 18(4), 700-789.
 [http://dx.doi.org/10.1002/alz.12638] [PMID:  35289055]

[3]
Dementia.  Available from: https://www.who.int/news-room/fact-sheets/detail/dementia (cited 2023 Sep 4).

[4]
Avila, J.; Hernández, F. GSK-3 inhibitors for Alzheimer’s disease. Expert Rev. Neurother.,  2007, 7(11), 1527-1533.
 [http://dx.doi.org/10.1586/14737175.7.11.1527] [PMID:  17997701]

[5]
Tahami Monfared, A.A.; Byrnes, M.J.; White, L.A.; Zhang, Q. The humanistic and economic burden of alzheimer’s Disease. Neurol. Ther.,  2022, 11(2), 525-551.
 [http://dx.doi.org/10.1007/s40120-022-00335-x] [PMID:  35192176]

[6]
Zhu, C.W.; Sano, M. Economic considerations in the management of Alzheimer’s disease. Clin. Interv. Aging,  2006, 1(2), 143-154.
 [http://dx.doi.org/10.2147/ciia.2006.1.2.143] [PMID:  18044111]

[7]
Rampa, A.; Gobbi, S.; Concetta Di Martino, R.M.; Belluti, F.; Bisi, A. Dual BACE-1/GSK-3β inhibitors to combat alzheimer’s disease: A focused review. Curr. Top. Med. Chem.,  2018, 17(31), 3361-3369.
 [http://dx.doi.org/10.2174/1568026618666180112161406]

[8]
Goedert, M.; Spillantini, M.G. A century of Alzheimer’s disease. Science,  2006, 314(5800), 777-781.
 [http://dx.doi.org/10.1126/science.1132814] [PMID:  17082447]

[9]
Hernández, F.; Gómez de Barreda, E.; Fuster-Matanzo, A.; Lucas, J.J.; Avila, J. GSK3: A possible link between beta amyloid peptide and tau protein. Exp. Neurol.,  2010, 223(2), 322-325.
 [http://dx.doi.org/10.1016/j.expneurol.2009.09.011] [PMID:  19782073]

[10]
Bloom, G.S. Amyloid-β and Tau. JAMA Neurol.,  2014, 71(4), 505-508.
 [http://dx.doi.org/10.1001/jamaneurol.2013.5847] [PMID:  24493463]

[11]
Nisbet, R.M.; Götz, J. Amyloid-β and Tau in alzheimer’s disease: Novel pathomechanisms and non-pharmacological treatment strategies. J. Alzheimers Dis.,  2018, 64(s1), S517-S527.
 [http://dx.doi.org/10.3233/JAD-179907] [PMID:  29562514]

[12]
Busche, M.A.; Hyman, B.T. Synergy between amyloid-β and tau in Alzheimer’s disease. Nat. Neurosci.,  2020, 23(10), 1183-1193.
 [http://dx.doi.org/10.1038/s41593-020-0687-6] [PMID:  32778792]

[13]
Cavalli, A.; Bolognesi, M.L.; Minarini, A.; Rosini, M.; Tumiatti, V.; Recanatini, M.; Melchiorre, C. Multi-target-directed ligands to combat neurodegenerative diseases. J. Med. Chem.,  2008, 51(3), 347-372.
 [http://dx.doi.org/10.1021/jm7009364] [PMID:  18181565]

[14]
Csermely, P.; Agoston, V.; Pongor, S. The efficiency of multi-target drugs: the network approach might help drug design. Trends Pharmacol. Sci.,  2005, 26(4), 178-182.
 [http://dx.doi.org/10.1016/j.tips.2005.02.007] [PMID:  15808341]

[15]
Hughes, R.E.; Nikolic, K.; Ramsay, R.R. One for all? hitting multiple alzheimer’s disease targets with one drug. Front. Neurosci.,  2016, 10, 177.
 [http://dx.doi.org/10.3389/fnins.2016.00177] [PMID:  27199640]

[16]
León, R.; Garcia, A.G.; Marco-Contelles, J. Recent advances in the multitarget-directed ligands approach for the treatment of Alzheimer’s disease. Med. Res. Rev.,  2013, 33(1), 139-189.
 [http://dx.doi.org/10.1002/med.20248] [PMID:  21793014]

[17]
Teli, P.; Sahiba, N.; Soni, J.; Sethiya, A.; Agarwal, D.K.; Agarwal, S. Exploration of potent multi-target-directed-ligands as anti-alzheimer’s disease agents: A moiety based review. Mini Rev. Med. Chem.,  2021, 21(20), 3219-3248.
 [http://dx.doi.org/10.2174/1389557521666210304111754] [PMID:  33663363]

[18]
Das, S.; Basu, S. Multi-targeting strategies for alzheimer’s disease therapeutics: Pros and Cons. Curr. Top. Med. Chem.,  2017, 17(27), 3017-3061.
 [PMID:  28685694]

[19]
Coimbra, J.R.M.; Marques, D.F.F.; Baptista, S.J.; Pereira, C.M.F.; Moreira, P.I.; Dinis, T.C.P.; Santos, A.E.; Salvador, J.A.R. Highlights in BACE1 Inhibitors for Alzheimer’s Disease Treatment. Front Chem.,  2018, 6, 178.
 [http://dx.doi.org/10.3389/fchem.2018.00178] [PMID:  29881722]

[20]
Das, B.; Yan, R. A close look at BACE1 inhibitors for alzheimer’s disease treatment. CNS Drugs,  2019, 33(3), 251-263.
 [http://dx.doi.org/10.1007/s40263-019-00613-7] [PMID:  30830576]

[21]
Ghosh, A.K.; Osswald, H.L. BACE1 (β-secretase) inhibitors for the treatment of Alzheimer’s disease. Chem. Soc. Rev.,  2014, 43(19), 6765-6813.
 [http://dx.doi.org/10.1039/C3CS60460H] [PMID:  24691405]

[22]
Guo, T.; Hobbs, D. Development of BACE1 inhibitors for Alzheimer’s disease. Curr. Med. Chem.,  2006, 13(15), 1811-1829.
 [http://dx.doi.org/10.2174/092986706777452489] [PMID:  16787223]

[23]
Hu, X.; Hicks, C.W.; He, W.; Wong, P.; Macklin, W.B.; Trapp, B.D.; Yan, R. Bace1 modulates myelination in the central and peripheral nervous system. Nat. Neurosci.,  2006, 9(12), 1520-1525.
 [http://dx.doi.org/10.1038/nn1797] [PMID:  17099708]

[24]
Leroy, K.; Yilmaz, Z.; Brion, J.P. Increased level of active GSK-3? in Alzheimer’s disease and accumulation in argyrophilic grains and in neurones at different stages of neurofibrillary degeneration. Neuropathol. Appl. Neurobiol.,  2007, 33(1), 43-55.
 [http://dx.doi.org/10.1111/j.1365-2990.2006.00795.x] [PMID:  17239007]

[25]
Eldar-Finkelman, H.; Martinez, A. GSK-3 inhibitors: Preclinical and clinical focus on CNS. Front. Mol. Neurosci.,  2011, 4, 32.
 [http://dx.doi.org/10.3389/fnmol.2011.00032] [PMID:  22065134]

[26]
Eldar-Finkelman, H.; Licht-Murava, A.; Pietrokovski, S.; Eisenstein, M. Substrate competitive GSK-3 inhibitors: Strategy and implications. Biochim. Biophys. Acta. Proteins Proteomics,  2010, 1804(3), 598-603.
 [http://dx.doi.org/10.1016/j.bbapap.2009.09.010] [PMID:  19770076]

[27]
Llorens-Martín, M.; Jurado, J.; Hernández, F.; Avila, J. GSK-3β, a pivotal kinase in Alzheimer disease. Front. Mol. Neurosci.,  2014, 7, 46.
 [http://dx.doi.org/10.3389/fnmol.2014.00046]

[28]
Doble, B.W.; Woodgett, J.R. GSK-3: Tricks of the trade for a multi-tasking kinase. J. Cell Sci.,  2003, 116(7), 1175-1186.
 [http://dx.doi.org/10.1242/jcs.00384] [PMID:  12615961]

[29]
Kypta, R.M. GSK-3 inhibitors and their potential in the treatment of Alzheimer’s disease. Expert Opin. Ther. Pat.,  2005, 15(10), 1315-1331.
 [http://dx.doi.org/10.1517/13543776.15.10.1315]

[30]
Lei, P.; Ayton, S.; Bush, A.I.; Adlard, P.A. GSK-3 in neurodegenerative diseases. Int. J. Alzheimers Dis.,  2011, 2011, 1-9.
 [http://dx.doi.org/10.4061/2011/189246] [PMID:  21629738]

[31]
Paudel, P.; Seong, S.H.; Zhou, Y.; Ha, M.T.; Min, B.S.; Jung, H.A.; Choi, J.S. Arylbenzofurans from the Root Bark of Morus alba as triple inhibitors of cholinesterase, β-site amyloid precursor protein cleaving enzyme 1, and glycogen synthase kinase-3β: Relevance to alzheimer’s disease. ACS Omega,  2019, 4(4), 6283-6294.
 [http://dx.doi.org/10.1021/acsomega.9b00198] [PMID:  31459768]

[32]
Jiang, X.; Lu, H.; Li, J.; Liu, W.; Wu, Q.; Xu, Z.; Qiao, Q.; Zhang, H.; Gao, H.; Zhao, Q. A natural BACE1 and GSK3β dual inhibitor Notopterol effectively ameliorates the cognitive deficits in APP/PS1 Alzheimer’s mice by attenuating amyloid‐β and tau pathology. Clin. Transl. Med.,  2020, 10(3), e50.
 [http://dx.doi.org/10.1002/ctm2.50] [PMID:  32652879]

[33]
Di Martino, R.M.C.; De Simone, A.; Andrisano, V.; Bisignano, P.; Bisi, A.; Gobbi, S.; Rampa, A.; Fato, R.; Bergamini, C.; Perez, D.I.; Martinez, A.; Bottegoni, G.; Cavalli, A.; Belluti, F. Versatility of the curcumin scaffold: Discovery of potent and balanced dual BACE-1 and GSK-3β inhibitors. J. Med. Chem.,  2016, 59(2), 531-544.
 [http://dx.doi.org/10.1021/acs.jmedchem.5b00894] [PMID:  26696252]

[34]
Prati, F.; De Simone, A.; Bisignano, P.; Armirotti, A.; Summa, M.; Pizzirani, D.; Scarpelli, R.; Perez, D.I.; Andrisano, V.; Perez-Castillo, A.; Monti, B.; Massenzio, F.; Polito, L.; Racchi, M.; Favia, A.D.; Bottegoni, G.; Martinez, A.; Bolognesi, M.L.; Cavalli, A. Multitarget drug discovery for Alzheimer’s disease: Triazinones as BACE-1 and GSK-3β inhibitors. Angew. Chem. Int. Ed.,  2015, 54(5), 1578-1582.
 [http://dx.doi.org/10.1002/anie.201410456] [PMID:  25504761]

[35]
Prati, F.; De Simone, A.; Armirotti, A.; Summa, M.; Pizzirani, D.; Scarpelli, R.; Bertozzi, S.M.; Perez, D.I.; Andrisano, V.; Perez-Castillo, A.; Monti, B.; Massenzio, F.; Polito, L.; Racchi, M.; Sabatino, P.; Bottegoni, G.; Martinez, A.; Cavalli, A.; Bolognesi, M.L. 3,4-Dihydro-1,3,5-triazin-2(1 H)-ones as the First Dual BACE-1/GSK-3β Fragment Hits against Alzheimer’s Disease. ACS Chem. Neurosci.,  2015, 6(10), 1665-1682.
 [http://dx.doi.org/10.1021/acschemneuro.5b00121] [PMID:  26171616]

[36]
Cole, S.; Vassar, R. BACE1 structure and function in health and Alzheimer’s disease. Curr. Alzheimer Res.,  2008, 5(2), 100-120.
 [http://dx.doi.org/10.2174/156720508783954758] [PMID:  18393796]

[37]
Vassar, R. The β-secretase, BACE: A prime drug target for Alzheimer’s disease. J. Mol. Neurosci.,  2001, 17(2), 157-170.
 [http://dx.doi.org/10.1385/JMN:17:2:157] [PMID:  11816789]

[38]
Huang, W.H.; Sheng, R.; Hu, Y.Z. Progress in the development of nonpeptidomimetic BACE 1 inhibitors for Alzheimer’s disease. Curr. Med. Chem.,  2009, 16(14), 1806-1820.
 [http://dx.doi.org/10.2174/092986709788186174] [PMID:  19442147]

[39]
Kumar, A.; Srivastava, G.; Negi, A.S.; Sharma, A. Docking, molecular dynamics, binding energy-MM-PBSA studies of naphthofuran derivatives to identify potential dual inhibitors against BACE-1 and GSK-3β. J. Biomol. Struct. Dyn.,  2019, 37(2), 275-290.
 [http://dx.doi.org/10.1080/07391102.2018.1426043] [PMID:  29310523]

[40]
Machauer, R.; Lueoend, R.; Hurth, K.; Veenstra, S.J.; Rueeger, H.; Voegtle, M.; Tintelnot-Blomley, M.; Rondeau, J.M.; Jacobson, L.H.; Laue, G.; Beltz, K.; Neumann, U. Discovery of Umibecestat (CNP520): A potent, selective, and efficacious β-secretase (BACE1) inhibitor for the prevention of alzheimer’s disease. J. Med. Chem.,  2021, 64(20), 15262-15279.
 [http://dx.doi.org/10.1021/acs.jmedchem.1c01300] [PMID:  34648711]

[41]
Hong, L.; Tang, J. Flap position of free memapsin 2 (β-secretase), a model for flap opening in aspartic protease catalysis. Biochemistry,  2004, 43(16), 4689-4695.
 [http://dx.doi.org/10.1021/bi0498252] [PMID:  15096037]

[42]
Barman, A.; Schürer, S.; Prabhakar, R. Computational modeling of substrate specificity and catalysis of the β-secretase (BACE1) enzyme. Biochemistry,  2011, 50(20), 4337-4349.
 [http://dx.doi.org/10.1021/bi200081h] [PMID:  21500768]

[43]
Fujimoto, K.; Matsuoka, E.; Asada, N.; Tadano, G.; Yamamoto, T.; Nakahara, K.; Fuchino, K.; Ito, H.; Kanegawa, N.; Moechars, D.; Gijsen, H.J.M.; Kusakabe, K. Structure-based design of selective β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors: Targeting the flap to gain selectivity over BACE2. J. Med. Chem.,  2019, 62(10), 5080-5095.
 [http://dx.doi.org/10.1021/acs.jmedchem.9b00309] [PMID:  31021626]

[44]
Yuan, J.; Venkatraman, S.; Zheng, Y.; McKeever, B.M.; Dillard, L.W.; Singh, S.B. Structure-based design of β-site APP cleaving enzyme 1 (BACE1) inhibitors for the treatment of Alzheimer’s disease. J. Med. Chem.,  2013, 56(11), 4156-4180.
 [http://dx.doi.org/10.1021/jm301659n] [PMID:  23509904]

[45]
Buch, I.; Fishelovitch, D.; London, N.; Raveh, B.; Wolfson, H.J.; Nussinov, R. Allosteric regulation of glycogen synthase kinase 3β: A theoretical study. Biochemistry,  2010, 49(51), 10890-10901.
 [http://dx.doi.org/10.1021/bi100822q] [PMID:  21105670]

[46]
Elangovan, N.D.; Dhanabalan, A.K.; Gunasekaran, K.; Kandimalla, R.; Sankarganesh, D. Screening of potential drug for Alzheimer’s disease: A computational study with GSK-3 β inhibition through virtual screening, docking, and molecular dynamics simulation. J. Biomol. Struct. Dyn.,  2021, 39(18), 7065-7079.
 [http://dx.doi.org/10.1080/07391102.2020.1805362] [PMID:  32779973]

[47]
He, Q.; Han, C.; Li, G.; Guo, H.; Wang, Y.; Hu, Y.; Lin, Z.; Wang, Y. In silico design novel (5-imidazol-2-yl-4-phenylpyrimidin-2-yl)[2-(2-pyridylamino)ethyl]amine derivatives as inhibitors for glycogen synthase kinase 3 based on 3D-QSAR, molecular docking and molecular dynamics simulation. Comput. Biol. Chem.,  2020, 88, 107328.
 [http://dx.doi.org/10.1016/j.compbiolchem.2020.107328] [PMID:  32688011]

[48]
Nassar, H.; Sippl, W.; Dahab, R.A.; Taha, M. Molecular docking, molecular dynamics simulations and in vitro screening reveal cefixime and ceftriaxone as GSK3β covalent inhibitors. RSC Adv.,  2023, 13(17), 11278-11290.
 [http://dx.doi.org/10.1039/D3RA01145C] [PMID:  37057264]

[49]
Ghosh, S.; Keretsu, S.; Cho, S.J. 3D-QSAR, docking and molecular dynamics simulation study of C-Glycosylflavones as GSK-3&#946; inhibitors. J. Chosun. Nat. Sci.,  2020, 13(4), 170-180.

[50]
Kumar, A.; Srivastava, G.; Srivastava, S.; Verma, S.; Negi, A.S.; Sharma, A. Investigation of naphthofuran moiety as potential dual inhibitor against BACE-1 and GSK-3β: Molecular dynamics simulations, binding energy, and network analysis to identify first-in-class dual inhibitors against Alzheimer’s disease. J. Mol. Model.,  2017, 23(8), 239.
 [http://dx.doi.org/10.1007/s00894-017-3396-7] [PMID:  28741112]

[51]
Kumar, A.; Srivastava, G.; Sharma, A. In silico interaction studies of first dual inhibitor against BACE-1/GSK-3β. In: 2016 International Conference on Bioinformatics and Systems Biology (BSB).,  2016, pp. 1-4.
 [http://dx.doi.org/10.1109/BSB.2016.7552161]

[52]
ZINC.  Available from: https://zinc15.docking.org/substances/subsets/ (cited 2023 Sep 3).

[53]
Chapter 18. Discovery of Multi-Target Agents for Neurological Diseases via Ligand Design | Request PDF.  Available from: https://www.researchgate.net/publication/346791653_Chapter_18_Discovery_of_Multi-Target_Agents_for_Neurological_Diseases_via_Ligand_Design (cited 2023 Sep 3).

[54]
Domínguez, J.L.; Fernández-Nieto, F.; Castro, M.; Catto, M.; Paleo, M.R.; Porto, S.; Sardina, F.J.; Brea, J.M.; Carotti, A.; Villaverde, M.C.; Sussman, F. Computer-aided structure-based design of multitarget leads for Alzheimer’s disease. J. Chem. Inf. Model.,  2015, 55(1), 135-148.
 [http://dx.doi.org/10.1021/ci500555g] [PMID:  25483751]

[55]
Raj, U.; Kumar, H.; Gupta, S.; Varadwaj, P.K. Exploring dual inhibitors for STAT1 and STAT5 receptors utilizing virtual screening and dynamics simulation validation. J. Biomol. Struct. Dyn.,  2016, 34(10), 2115-2129.
 [http://dx.doi.org/10.1080/07391102.2015.1108870] [PMID:  26471877]

[56]
Ramsay, R.R.; Majekova, M.; Medina, M.; Valoti, M. Key targets for multi-target ligands designed to combat neurodegeneration. Front. Neurosci.,  2016, 10, 375.
 [http://dx.doi.org/10.3389/fnins.2016.00375] [PMID:  27597816]

[57]
Pirolli, D.; Righino, B.; Camponeschi, C.; Ria, F.; Di Sante, G.; De Rosa, M.C. Virtual screening and molecular dynamics simulations provide insight into repurposing drugs against SARS-CoV-2 variants Spike protein/ACE2 interface. Sci. Rep.,  2023, 13(1), 1494.
 [http://dx.doi.org/10.1038/s41598-023-28716-8] [PMID:  36707679]

[58]
Chander, S.; Pandey, R.K.; Penta, A.; Choudhary, B.S.; Sharma, M.; Malik, R.; Prajapati, V.K.; Murugesan, S. Molecular docking and molecular dynamics simulation based approach to explore the dual inhibitor against HIV-1 reverse transcriptase and integrase. Comb. Chem. High Throughput Screen.,  2017, 20(8), 734-746.
 [PMID:  28641512]

[59]
Manandhar, S.; Pai, K.S.R.; Krishnamurthy, P.T.; Kiran, A.V.V.V.R.; Kumari, G.K. Identification of novel TMPRSS2 inhibitors against SARS-CoV-2 infection: A structure-based virtual screening and molecular dynamics study. Struct. Chem.,  2022, 33(5), 1529-1541.
 [http://dx.doi.org/10.1007/s11224-022-01921-3] [PMID:  35345416]

[60]
Baby, K.; Maity, S.; Mehta, C.H.; Suresh, A.; Nayak, U.Y.; Nayak, Y. SARS-CoV-2 entry inhibitors by dual targeting TMPRSS2 and ACE2: An in silico drug repurposing study. Eur. J. Pharmacol.,  2021, 896, 173922.
 [http://dx.doi.org/10.1016/j.ejphar.2021.173922] [PMID:  33539819]

[61]
Ivanova, L.; Tammiku-Taul, J.; García-Sosa, A.T.; Sidorova, Y.; Saarma, M.; Karelson, M. Molecular dynamics simulations of the interactions between glial cell line-derived neurotrophic factor family receptor GFRα1 and small-molecule ligands. ACS Omega,  2018, 3(9), 11407-11414.
 [http://dx.doi.org/10.1021/acsomega.8b01524] [PMID:  30320260]

[62]
Docking of FDA Approved Drugs Targeting NSP-16. Docking of FDA Approved Drugs Targeting NSP-16, N-Protein and Main Protease of SARS-CoV-2 as Dual Inhibitors. Biointerface Res. Appl. Chem.,  2020, 11(3), 9848-9861.
 [http://dx.doi.org/10.33263/BRIAC113.98489861]

[63]
P, G.; M K, K. Docking studies and molecular dynamics simulation of triazole benzene sulfonamide derivatives with human carbonic anhydrase IX inhibition activity. RSC Adv.,  2021, 11(60), 38079-38093.
 [http://dx.doi.org/10.1039/D1RA07377J] [PMID:  35498092]

[64]
Nawaz, M.Z.; Attique, S.A.; Ain, Q.; Alghamdi, H.A.; Bilal, M.; Yan, W.; Zhu, D. Discovery and characterization of dual inhibitors of human Vanin-1 and Vanin-2 enzymes through molecular docking and dynamic simulation-based approach. Int. J. Biol. Macromol.,  2022, 213, 1088-1097.
 [http://dx.doi.org/10.1016/j.ijbiomac.2022.06.014] [PMID:  35697166]

[65]
Krishna Swaroop, A.; Krishnan Namboori, P.K.; Esakkimuthukumar, M.; Praveen, T.K.; Nagarjuna, P.; Patnaik, S.K.; Selvaraj, J. Leveraging decagonal in-silico strategies for uncovering IL-6 inhibitors with precision. Comput. Biol. Med.,  2023, 163, 107231.
 [http://dx.doi.org/10.1016/j.compbiomed.2023.107231] [PMID:  37421735]

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DOI https://dx.doi.org/10.2174/0115734099270256231018072007	Print ISSN 1573-4099
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Rational Design of Dual Inhibitors for Alzheimer's Disease: Insights from Computational Screening of BACE1 and GSK-3β

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