In silico methods to assist drug developers in acetylcholinesterase inhibitor design

Current Medicinal Chemistry

Volumn 18, Issue 8, 2011, Pages 1122-1136

  Bermudez Lugo J A ^a   Rosales Hernandez M C ^a   Deeb, O ^b   Trujillo Ferrara, J ^a   Correa Basurto, J ^a  

^a INSTITUTO POLITÉCNICO NACIONAL   (Mexico)

^b AL QUDS UNIVERSITY   (Palestine)

Author keywords

Acetylcholinesterase; Docking; In silico methods; Molecular dynamics; Sequence alignment

Indexed keywords

CHOLINESTERASE INHIBITOR;

ALZHEIMER DISEASE; ARTIFICIAL NEURAL NETWORK; BINDING AFFINITY; COMPUTER MODEL; COMPUTER PREDICTION; COMPUTER SIMULATION; DRUG BINDING SITE; DRUG DESIGN; DRUG SYNTHESIS; ENZYME INHIBITION; ENZYME SPECIFICITY; HUMAN; MOLECULAR DOCKING; MOLECULAR DYNAMICS; MULTIPLE LINEAR REGRESSION ANALYSIS; MYASTHENIA GRAVIS; NONHUMAN; PARTITION COEFFICIENT; PHYSICAL CHEMISTRY; QUANTITATIVE STRUCTURE ACTIVITY RELATION; QUANTUM CHEMISTRY; QUANTUM MECHANICS; REVIEW; SEQUENCE ALIGNMENT; STRUCTURAL BIOINFORMATICS; SUPPORT VECTOR MACHINE;

ACETYLCHOLINE; ACETYLCHOLINESTERASE; ANIMALS; CHOLINESTERASE INHIBITORS; DRUG DESIGN; HUMANS; HYDROLYSIS; MOLECULAR DYNAMICS SIMULATION; QUANTUM THEORY; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 79952779846     PISSN: 09298673     EISSN: None     Source Type: Journal    
DOI: 10.2174/092986711795029681     Document Type: Review

References (142)

1. Lage, J.M. 100 years of Alzheimer's disease (1906-2006). J. Alzheimers Dis., 2006, 9(3 Suppl), 15-26. (Pubitemid 44253294)
2. Herbert, L.E.; Beckett, L.A.; Scherr, P.A.; Evans, D.A. Annual incidence of Alzheimer disease in the United States projected to the years 2000 through 2050. Alzheimer Dis. Assoc. Disord., 2001, 15, 169-173. (Pubitemid 33117032)
3. Guillozet, A.L.; Weintraub, S.; Mash, D.C.; Mesulam, M.M. Neurofibrillary tangles, amyloid, and memory in aging and mild cognitive impairment. Arch. Neurol., 2003, 60, 729-736. (Pubitemid 36569891)
4. Raschetti, R.; Albanese, E.; Vanacore, N.; Maggini, M. Cholinesterase inhibitors in mild cognitive impairment: A systematic review of randomised trials. PloS. Med., 2007, 4, e338.
5. Esiri, M. The basis for behavioural disturbances in dementia. J. Neurol. Neurosurg. Psychiatry, 1996, 61, 127-130. (Pubitemid 26264319)
6. Lahiri, D.K.; Alley, G.M.; Tweedie, D.; Chen, D.; Greig, N.H. Differential effects of two hexahydropyrroloindole carbamate-based anticholinesterase drugs on the amyloid beta protein pathway involved in Alzheimer's disease. Neuromol. Med., 2007, 9, 157-168. (Pubitemid 47065543)
7. Bachurin, S.O. Medicinal chemistry approaches for the treatment and prevention of Alzheimer's disease. Med. Res. Rev., 2003, 23, 48-88. (Pubitemid 36024908)
8. Abdesalam, E.B. Neurotoxic potential of six organophosphorus compounds in adult hens. Vet. Hum. Toxicol., 1999, 41, 290-292.
9. Cao, C.J.; Mioduszewski, R.J.; Menking, D.E.; Valdes, J.J.; Katz, E.J.; Eldefrawi, M.E.; Eldefrawi, A.T. Cytotoxicity of organophosphate anticholinesterase. In vitro Cell Dev. Biol. Anim., 1999, 35, 493-500.
10. Bourne, Y.; Grassi, J.; Bougis, P.E.; Marchot, P. Conformational flexibility of the acetylcholinesterase tetramer suggested by x-ray crystallography. J. Biol. Chem., 1999, 274, 30370-30376.
11. Khan, M.T. Molecular interactions of cholinesterases inhibitors using in silico methods: Current status and future prospects. N. Biotechnal., 2009, 25, 331-346.
12. Schwarz, M.; Glick, D.; Loewenstein, Y.; Soreq, H. Engineering of human cholinesterases explains and predicts diverse consequences of administration of various drugs and poisons. Pharmacol. Ther., 1995, 67, 283-322.
13. Sussman, J.L.; Harel, M.; Silman, I. Three-dimensional structure of acetylcholinesterase and of its complexes with anticholinesterase drugs. Chem. Biol. Interact., 1993, 87, 187-197. (Pubitemid 23205379)
14. Felder, C.E.; Botti, S.A.; Lifson, S.; Silman, I.; Sussman, J.L. External and internal electrostatic potentials of cholinesterase models. J. Mol. Graph. Model., 1997, 15, 318-327. (Pubitemid 28312651)
15. Langley, J.N.; Kato, T. The physiological action of physostigmine and its action on denervated skeletal muscle. J. Physiol., 1915, 49, 410-431.
16. Karczmar, A. Invited review: Anticholinesterases: Dramatic aspects of their use and misuse. Neurochem. Int., 1998, 32, 401-411. (Pubitemid 28287192)
17. Kaur, J.; Zhang, M.Q. Molecular modelling and QSAR of reversible acetylcholinesterase inhibitors. Curr. Med. Chem., 2000, 7, 273-294. (Pubitemid 30396439)
18. Correa-Basurto, J.; Espinosa-Raya, J.; González-May, M.; Espinoza- Fonseca, L.M.; Vázquez-Alcántara, I.; Trujillo-Ferrara, J. Inhibition of acetylcholinesterase by two arylderivatives: 3a-Acetoxy-5H-pyrrolo (1,2-a) (3, 1)benzoxazin- 1,5-(3aH)-dione and cis-N-p-Acetoxy- phenylisomaleimide. J. Enzyme Inhib. Med. Chem., 2006, 21, 133-138. (Pubitemid 44083963)
19. Huey, R.; Morris, G.M.; Olson, A.J.; Goodsell, D.S. A semiempirical free energy force field with charge-based desolvation. J. Comput. Chem., 2007, 28, 1145-1152. (Pubitemid 46506716)
20. Deeb, O.; Rosales-Hernández, M.C.; Gómez-Castro, C.; Garduño-Juárez, R.; Correa-Basurto, J. Exploration of human serum albumin binding sites by docking and molecular dynamics flexible ligand-protein interactions. Biopolymers, 2010, 93, 161-170.
21. Eichler, J.; Anselment, A.; Sussman, J.L.; Massoulié, J.; Silman, I. Differential effects of "peripheral" site ligands on Torpedo and chicken acetylcholinesterase. Mol. Pharmacol., 1994, 45, 335-340.
22. Rose, G.D.; Fleming, P.J.; Banavar, J.R.; Maritan, A. A backbone-based theory of protein folding. Proc. Natl. Acad. Sci. U S A., 2006, 103, 16623-16633. (Pubitemid 44737304)
23. Cygler, M.; Schrag, J.D.; Sussman, J.L.; Harel, M.; Silman, I.; Gentry, M.K.; Doctor, B.P. Relationship between sequence conservation and threedimensional structure in a large family of esterases, lipases, and related proteins. Protein Sci., 1993, 2, 366-382. (Pubitemid 23071285)
24. Johnson, G.; Moore, S.W. Acetylcholinesterase readthrough peptide shares sequence similarity to the 28-53 peptide sequence of the acetylcholinesterase adhesion-mediating site and competes for ligand binding in vitro. J. Mol. Neurosci. 2007, 31, 113-126.
25. Wong, D.M.; Greenblatt, H.M.; Dvir, H.; Carlier, P.R.; Han, Y.F.; Pang, Y.P.; Silman, I.; Sussman, J.L. Acetylcholinesterase complexed with bivalent ligands related to huperzine a: Experimental evidence for species-dependent protein-ligand complementarity. J. Am. Chem. Soc., 2003, 125, 363-373. (Pubitemid 36077856)
26. Peterson, G.L. Consensus residues at the acetylcholine binding site of cholinergic proteins. J. Neurosci. Res., 1989, 22, 488-503. (Pubitemid 19145632)
27. Dhaliwal, B.; Chen, Y.W. Computational resources for protein modeling and drug discovery applications. Infect. Disord. Drug Targets. 2009, 5, 557-562.
28. Jain, A.N. Virtual screening in lead discovery and optimization. Curr. Opin. Drug Discov. Devel., 2004, 7, 396-403.
29. Sousa, S.F.; Fernandez, P.A.; Ramos, M.J. Protein-Ligand Docking: Current status and future challenges. Proteins, 2006, 65, 15-26. (Pubitemid 44320611)
30. Morris, G.M.; Goodsell, D.S.; Halliday, R.S.; Huey. R.; Hart, E.H.; Belew, R.K.; Olson, A.J. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J. Comput. Chem. 1998, 19, 1639-1662. (Pubitemid 128590223)
31. Yamamoto, Y.; Ishihara, Y; Kuntz, I.D. Docking analysis of a series of benzylamino acetylcholinesterase inhibitors with a phthalimide, benzoyl, or indanone moiety. J. Med. Chem. 1994, 37, 3141-3153. (Pubitemid 24317560)
32. Pang, Y.P.; Kozikowski, A.P. Prediction of the binding sites of huperzine A in acetylcholinesterase by docking studies. J. Comput. Aided Mol. Des., 1994, 8, 669-681.
33. Van den Born, H.K.; Radić, Z.; Marchot, P., Taylor, P.; Tsigelny, I. Theoretical analysis of the structure of the peptide fasciculin and its docking to acetylcholinesterase. Protein Sci., 1995, 4, 703-715.
34. Hosea, N.A.; Radić, Z.; Tsigelny, I.; Berman, H.A.; Quinn, D.M.; Taylor, P. Aspartate 74 as a primary determinant in acetylcholinesterase governing specificity to cationic organophosphonates. Biochemistry, 1996, 35, 10995-11004. (Pubitemid 26279683)
35. Silman, I.; Millard, C.B.; Ordentlich, A.; Greenblatt, H.M.; Harel, M.; Barak, D.; Shafferman, A.; Sussman, J.L. A preliminary comparison of structural models for catalytic intermediates of acetylcholinesterase. Chem. Biol. Interact., 1999, 119, 43-52. (Pubitemid 29278537)
36. Kovarik, Z.; Radić, Z.; Grgas, B.; Skrinjarić-Spoljar, M.; Reiner, E.; Simeon- Rudolf, V. Amino acid residues involved in the interaction of acetylcholinesterase and butyrylcholinesterase with the carbamates Ro 02-0683 and bambuterol, and with terbutaline. Biochim. Biophys. Acta., 1999, 1433, 261-271. (Pubitemid 29369061)
37. Bartolucci, C.; Perola, E.; Pilger, C.; Fels, G.; Lamba, D. Three-dimensional structure of a complex of galanthamine (Nivalin) with acetylcholinesterase from Torpedo californica: Implications for the design of new anti-Alzheimer drugs. Proteins, 2001, 42, 182-191. (Pubitemid 32047326)
38. Guo, C.Z.; Wu, J.H.; Wang, Y.X.; Hu, Y.D.; Li, S.; Sun, M.J. Molecular simulation of a single-chain antibody against AChE to explore molecular basis of inhibitory effect of 3F3 McAb on enzyme activity. Acta Pharmacol. Sin., 2003, 24, 460-466.
39. Choudhary, M.I.; Nawaz, S.A.; Zaheer-ul-Haq; Azim, M.K.; Ghayur, M.N.; Lodhi, M.A.; Jalil, S.; Khalid, A.; Ahmed, A.; Rode, B.M.; Atta-ur-Rahman; Gilani, A.U.; Ahmad, V.U. Juliflorine: A potent natural peripheral anionicsite- binding inhibitor of acetylcholinesterase with calcium-channel blocking potential, a leading candidate for Alzheimer's disease therapy. Biochem. Biophys. Res. Commun., 2005, 332, 1171-1177.
40. Dickerson, T.J.; Beuscher, A.E.4th.; Rogers, C.J.; Hixon, M.S.; Yamamoto, N.; Xu, Y.; Olson, A.J.; Janda, K.D. Discovery of acetylcholinesterase peripheral anionic site ligands through computational refinement of a directed library. Biochemistry, 2005, 44, 14845-14853. (Pubitemid 41612264)
41. Alisaraie, L.; Haller, L.A.; Fels, G. A QXP-based multistep docking procedure for accurate prediction of protein-ligand complexes. J. Chem. Inf. Model., 2006, 46, 1174-1187. (Pubitemid 43999162)
42. Odzak, R.; Calić, M.; Hrenar, T.; Primozic, I.; Kovarik, Z. Evaluation of monoquaternary pyridinium oximes potency to reactivate tabun-inhibited human acetylcholinesterase. Toxicology, 2007, 233, 85-96. (Pubitemid 46498373)
43. Rogers, C.J.; Eubanks, L.M.; Dickerson, T.J.; Janda, K.D. Unexpected acetylcholinesterase activity of cocaine esterases. J. Am. Chem. Soc., 2006, 128, 15364-15365. (Pubitemid 44875999)
44. Johnson, G.; Swart, C.; Moore, S.W. Non-enzymatic developmental functions of acetylcholinesterase-the question of redundancy. FEBS J., 2008, 275, 5129-5138.
45. Johnson, G.; Swart, C.; Moore, S.W. Interaction of acetylcholinesterase with the G4 domain of the laminin alpha1-chain. Biochem. J., 2008, 411, 507-514. (Pubitemid 351600735)
46. Bembenek, S.D.; Keith, J.M.; Letavic, M.A.; Apodaca, R.; Barbier, A.J.; Dvorak, L.; Aluisio, L.; Miller, K.L.; Lovenberg, T.W.; Carruthers, NI. Lead identification of acetylcholinesterase inhibitors-histamine H3 receptor antagonists from molecular modeling. Bioorg. Med. Chem., 2008, 16, 2968-2973. (Pubitemid 351418209)
47. Kawakami, Y.; Inoue, A.; Kawai, T.; Wakita, M.; Sugimoto, H.; Hopfinger, A.J. The rationale for E2020 as a potent acetylcholinesterase inhibitor. Bioorg. Med. Chem., 1996, 4, 1429-1446. (Pubitemid 26319994)
48. Inoue, A.; Kawai, T.; Wakita, M.; Iimura, Y.; Sugimoto, H.; Kawakami, Y. The simulated binding of (+/-)-2,3-dihydro-5,6-dimethoxy-2- [ [1- (phenylmethyl)-4-piperidinyl]meth yl] -1H-inden-1-one hydrochloride (E2020) and related inhibitors to free and acylated acetylcholinesterases and corresponding structure-activity analyses. J. Med. Chem., 1996, 39, 4460-4470. (Pubitemid 26359402)
49. Zeng, F.; Jiang, H.; Zhai, Y.; Zhang, H.; Chen, K.; Ji, R. Synthesis and acetylcholinesterase inhibitory activity of huperzine A-E2020 combined compound. Bioorg. Med. Chem. Lett., 1999, 9, 3279-3284.
50. Kwon, Y.E.; Park, J.Y.; No, K.T.; Shin, J.H.; Lee, S.K.; Eun, J.S.; Yang, J.; Shin, T.Y.; Kim, D.K.; Chae, B.S.; Leem, J.Y.; Kim, K.H. Synthesis, in vitro assay, and molecular modeling of new piperidine derivatives having dual inhibitory potency against acetylcholinesterase and Abeta1-42 aggregation for Alzheimer's disease therapeutics. Bioorg. Med. Chem., 2007, 15, 6596-6607. (Pubitemid 47302310)
51. Pang, Y.P.; Quiram, P.; Jelacic, T.; Hong, F.; Brimijoin, S. Highly potent, selective, and low cost bis-tetrahydroaminacrine inhibitors of acetylcholinesterase. Steps toward novel drugs for treating Alzheimer's disease. J. Biol. Chem., 1996, 271, 23646-23649.
52. Degen, S.J.; Mueller, K.L.; Shen, H.C.; Mulder, J.A.; Golding, G.M.; Wei, L.L.; Zificsak, C.A.; Neeno-Eckwall, A.; Hsung, R.P. Synthesis of dihydroxanthone derivatives and evaluation of their inhibitory activity against acetylcholinesterase: Unique structural analogs of tacrine based on the BCD-ring of arisugacin. Bioorg. Med. Chem. Lett., 1999, 9, 973-978. (Pubitemid 29179892)
53. Kapková, P.; Stiefl, N.; Sürig, U.; Engels, B.; Baumann, K.; Holzgrabe, U. Synthesis, biological activity, and docking studies of new acetylcholinesterase inhibitors of the bispyridinium type. Arch. Pharm., 2003, 336, 523-540. (Pubitemid 38005047)
54. Khalid, A.; Azim, M.K.; Parveen, S.; Atta-ur-Rahman.; Choudhary, M.I. Structural basis of acetylcholinesterase inhibition by triterpenoidal alkaloids. Biochem. Biophys. Res. Commun., 2005, 331, 1528-1532. (Pubitemid 40692528)
55. Sheng, R.; Lin, X.; Li, J.; Jiang, Y.; Shang, Z.; Hu, Y. Design, synthesis, and evaluation of 2-phenoxy-indan-1-one derivatives as acetylcholinesterase inhibitors. Bioorg. Med. Chem. Lett., 2005, 15, 3834-3837. (Pubitemid 41095478)
56. Choudhary, M.I.; Nawaz, S.A.; ul-Haq, Z.; Lodhi, M.A.; Ghayur, M.N.; Jalil, S.; Riaz, N.; Yousuf, S.; Malik, A.; Gilani, A.H.; ur-Rahman, A. Withanolides, a new class of natural cholinesterase inhibitors with calcium antagonistic properties. Biochem. Biophys. Res. Commun., 2005, 334, 276-287. (Pubitemid 40978536)
57. Xie, Q.; Tang, Y.; Li, W.; Wang, X.H.; Qiu, Z.B. Investigation of the binding mode of (-)-meptazinol and bis-meptazinol derivatives on acetylcholinesterase using a molecular docking method. J. Mol. Model., 2006, 12, 390-397. (Pubitemid 43337176)
58. da Silva, C.H.; Campo, V.L.; Carvalho, I.; Taft, C.A. Molecular modeling, docking and ADMET studies applied to the design of a novel hybrid for treatment of Alzheimer's disease. J. Mol. Graph. Model., 2006, 25, 169-175. (Pubitemid 44376630)
59. Rollinger, J.M.; Schuster, D.; Baier, E.; Ellmerer, E.P.; Langer, T.; Stuppner, H. Taspine: Bioactivity-guided isolation and molecular ligand-target insight of a potent acetylcholinesterase inhibitor from Magnolia x soulangiana. J. Nat. Prod., 2006, 69, 1341-1346. (Pubitemid 44568245)
60. Correa-Basurto, J.; Flores-Sandoval, C.; Marín-Cruz, J.; Rojo-Domínguez, A.; Espinoza-Fonseca, L.M.; Trujillo-Ferrara, J.G. Docking and quantum mechanic studies on cholinesterases and their inhibitors. Eur. J. Med. Chem., 2007, 42, 10-19. (Pubitemid 46201968)
61. Haviv, H.; Wong, D.M.; Silman, I.; Sussman, J.L. Bivalent ligands derived from Huperzine A as acetylcholinesterase inhibitors. Curr. Top Med. Chem., 2007, 7, 375-387. (Pubitemid 46358650)
62. He, X.C.; Feng, S.; Wang, Z.F., Shi, Y.; Zheng, S.; Xia, Y.; Jiang, H.; Tang, X.C.; Bai, D. Study on dual-site inhibitors of acetylcholinesterase: Highly potent derivatives of bis- and bifunctional huperzine B. Bioorg. Med. Chem., 2007, 15, 1394-1408. (Pubitemid 46049824)
63. Piazzi, L.; Cavalli, A.; Belluti, F.; Bisi, A.; Gobbi, S.; Rizzo, S.; Bartolini, M.; Andrisano, V.; Recanatini, M.; Rampa, A. Extensive SAR and computational studies of 3-{4- [(benzylmethylamino)methyl]phenyl}-6,7-dimethoxy- 2H-2-chromenone (AP2238) derivatives. J. Med. Chem., 2007, 50, 4250-4254. (Pubitemid 47301756)
64. Sauvaître, T.; Barlier, M.; Herlem, D.; Gresh, N.; Chiaroni, A.; Guenard, D.; Guillou, C. New potent acetylcholinesterase inhibitors in the tetracyclic triterpene series. J. Med. Chem., 2007, 50, 5311-5323. (Pubitemid 350057843)
65. Grigoryan, H.A.; Hambardzumyan, A.A.; Mkrtchyan, M.V.; Topuzyan, V.O.; Halebyan, G.P.; Asatryan, R.S. alpha,beta-Dehydrophenylalanine choline esters, a new class of reversible inhibitors of human acetylcholinesterase and butyrylcholinesterase. Chem. Biol. Interact., 2008, 171, 108-116. (Pubitemid 350191848)
66. Shen, L.L.; Liu, G.X.; Tang, Y. Molecular docking and 3D-QSAR studies of 2-substituted 1-indanone derivatives as acetylcholinesterase inhibitors. Acta Pharmacol. Sin., 2007, 28, 2053-2063. (Pubitemid 350198335)
67. Castro, N.G.; Costa, R.S.; Pimentel, L.S.; Danuello, A.; Romeiro, N.C.; Viegas, C. Jr.; Barreiro, E.J.; Fraga, C.A.; Bolzani, V.S.; Rocha, M.S. CNSselective noncompetitive cholinesterase inhibitors derived from the natural piperidine alkaloid (-)-spectaline. Eur. J. Pharmacol., 2008, 580, 339-349.
68. Xie, Q.; Wang, H.; Xia, Z.; Lu, M.; Zhang, W.; Wang, X.; Fu, W.; Tang, Y.; Sheng, W.; Li, W.; Zhou, W.; Zhu, X.; Qiu, Z.; Chen, H. Bis-(-)- normeptazinols as novel nanomolar cholinesterase inhibitors with high inhibitory potency on amyloid-beta aggregation. J. Med. Chem., 2008, 51, 2027-2036. (Pubitemid 351503258)
69. Nawaz, S.A.; Umbreen, S.; Kahlid, A.; Ansari, F.L.; Choudhary, M.I. Structural insight into the inhibition of acetylcholinesterase by 2,3,4, 5-tetrahydro- 1, 5-benzothiazepines. J. Enzyme Inhib. Med. Chem., 2008, 23, 206-212. (Pubitemid 351404839)
70. Pan, L.; Tan, J.H.; Hou, J.Q.; Huang, S.L.; Gu, L.Q.; Huang, Z.S. Design, synthesis and evaluation of isaindigotone derivatives as acetylcholinesterase and butyrylcholinesterase inhibitors. Bioorg. Med. Chem. Lett., 2008, 18, 3790-3793. (Pubitemid 351794508)
71. Nukoolkarn, V.S.; Saen-oon, S.; Rungrotmongkol, T.; Hannongbua, S.; Ingkaninan, K.; Suwanborirux, K. Petrosamine, a potent anticholinesterase pyridoacridine alkaloid from a Thai marine sponge Petrosia n. sp. Bioorg. Med. Chem., 2008, 16, 6560-6567.
72. Jia, P.; Sheng, R., Zhang, J.; Fang, L.; He, Q.; Yang, B.; Hu, Y. Design, synthesis and evaluation of galanthamine derivatives as acetylcholinesterase inhibitors. Eur. J. Med. Chem., 2009, 44, 772-784.
73. Leonetti, F.; Catto, M.; Nicolotti, O.; Pisani, L.; Cappa, A.; Stefanachi, A.; Carotti, A. Homo- and hetero-bivalent edrophonium-like ammonium salts as highly potent, dual binding site AChE inhibitors. Bioorg. Med. Chem., 2008, 16, 7450-7456.
74. Rizzo, S.; Cavalli, A.; Ceccarini, L.; Bartolini, M.; Belluti, F.; Bisi, A.; Andrisano, V.; Recanatini, M.; Rampa, A. Structure-activity relationships and binding mode in the human acetylcholinesterase active site of pseudoirreversible inhibitors related to xanthostigmine. ChemMedChem., 2009, 4, 670-679.
75. Tang, H.; Wei, Y.B.; Zhang, C.; Ning, F.X.; Qiao, W.; Huang, S.L.; Ma, L.; Huang, Z.S.; Gu, L.Q. Synthesis, biological evaluation and molecular modeling of oxoisoaporphine and oxoaporphine derivatives as new dual inhibitors of acetylcholinesterase/butyrylcholinesterase. Eur. J. Med. Chem., 2009, 44, 2523-2532.
76. Miezan-Ezoulin, J.M.; Shao, B.Y.; Xia, Z.; Xie, Q.; Li, J.; Cui, Y.Y.; Wang, H.; Dong, C.Z.; Zhao, Y.X.; Massicot, F.; Qiu, Z.B.; Heymans, F.; Chen, H.Z. Novel piperazine derivative PMS1339 exhibits tri-functional properties and cognitive improvement in mice. Int. J. Neuropsychopharmacol., 2009, 12, 1409-11419.
77. Girisha, H.R.; Narendra-Sharath-Chandra, J.N.; Boppana, S.; Malviya, M.; Sadashiva, C.T.; Rangappa, K.S. Active site directed docking studies: Synthesis and pharmacological evaluation of cis-2,6-dimethyl piperidine sulfonamides as inhibitors of acetylcholinesterase. Eur. J. Med. Chem., 2009, 44, 4057-4062.
78. Villalobos, A.; Blake, J.F.; Biggers, C.K.; Butler, T.W.; Chapin, D.S.; Chen, Y.L.; Ives, J.L.; Jones, S.B.; Liston, D.;, Nagel, A.A. Novel benzisoxazole derivatives as potent and selective inhibitors of acetylcholinesterase. J. Med. Chem., 1994, 37, 2721-2734. (Pubitemid 24273464)
79. Barril, X.; Orozco, M.; Luque, F.J. Predicting relative binding free energies of tacrine-huperzine A hybrids as inhibitors of acetylcholinesterase. J. Med. Chem., 1999, 42, 5110-5119. (Pubitemid 30020262)
80. Andreani, A.; Cavalli, A.; Granaiola, M.; Guardigli, M.; Leoni, A.; Locatelli, A.; Morigi, R.; Rambaldi, M.; Recanatini, M.; Roda, A. Synthesis and screening for antiacetylcholinesterase activity of (1-benzyl-4-oxopiperidin-3- ylidene)methylindoles and -pyrroles related to donepezil. J. Med. Chem., 2001, 44, 4011-4014. (Pubitemid 33051491)
81. Carbonell, T.; Masip, I.; Sánchez-Baeza, F.; Delgado, M.; Araya, E.; Llorens, O.; Corcho, F.; Pérez, J.J.; Pérez-Payá, E.; Messeguer, A. Identification of selective inhibitors of acetylcholinesterase from a combinatorial library of 2,5-piperazinediones. Mol. Divers., 2000, 5, 131-143. (Pubitemid 34847015)
82. Senapati, S.; Bui, J.M.; McCammon, J.A. Induced fit in mouse acetylcholinesterase upon binding a femtomolar inhibitor: A molecular dynamics study. J. Med. Chem., 2005, 48, 8155-8162. (Pubitemid 43032524)
83. Niu, C.; Xu, Y.; Xu, Y.; Luo, X.; Duan, W.; Silman, I.; Sussman, J.L.; Zhu, W.; Chen, K.; Shen, J.; Jiang, H. Dynamic mechanism of E2020 binding to acetylcholinesterase: A steered molecular dynamics simulation. J. Phys. Chem. B., 2005, 109, 23730-23738. (Pubitemid 43081549)
84. Hu, Z.J.; Jiang, H.L.; Chen, J.Z.; Chen, K.X.; Ji, R.Y. Analysis of electronic structures of physostigmine analogs. Zhonqquo YaoLi Xue Bao., 1998, 19, 322-326.
85. Daidone, I.; Neuweiler, H.; Doose, S.; Sauer, M.; Smith, J.C. Hydrogen-bond driven loop-closure kinetics in unfolded polypeptide chains. PLoS Comput. Biol., 2010, 6, e1000645.
86. Axelsen, P.H.; Harel, M.; Silman, I.; Sussman, J.L. Structure and dynamics of the active site gorge of acetylcholinesterase: Synergistic use of molecular dynamics simulation and X-ray crystallography. Protein Sci., 1994, 3, 188-197. (Pubitemid 24086352)
87. Gilson, M.K.; Straatsma, T.P.; McCammon, J.A.; Ripoll, D.R.; Faerman, C.H.; Axelsen, P.H.; Silman, I.; Sussman, J.L. Open "back door" in a molecular dynamics simulation of acetylcholinesterase. Science, 1994, 263, 1276-1278.
88. Zhou, H.X.; Wlodek, S.T.; McCammon, J.A. Conformation gating as a mechanism for enzyme specificity. Proc. Natl. Acad. Sci. U.S.A., 1998, 95, 9280-9283. (Pubitemid 28506222)
89. Shen, T.Y.; Tai, K.; McCammon, J.A. Statistical analysis of the fractal gating motions of the enzyme acetylcholinesterase. Phys. Rev. E. Stat. Nonlin. Soft Matter Phys., 2001, 63, 041902.
90. Tara, S.; Straatsma, T.P.; McCammon, J.A. Mouse acetylcholinesterase unliganded and in complex with huperzine A: A comparison of molecular dynamics simulations. Biopolymers, 1999, 50, 35-43. (Pubitemid 29246357)
91. Tara, S.; Helms, V.; Straatsma, T.P.; McCammon, J.A. Molecular dynamics of mouse acetylcholinesterase complexed with huperzine A. Biopolymers, 1999, 50, 347-359. (Pubitemid 29390076)
92. Enyedy, I.J.; Kovach, I.M.; Bencsura, A. Molecular dynamics study of active-site interactions with tetracoordinate transients in acetylcholinesterase and its mutants. Biochem. J., 2001, 353, 645-653. (Pubitemid 32158333)
93. Tai, K.; Shen, T.; Henchman, R.; Bourne, Y.; Marchot, P.; McCammon, J.A. Mechanism of acetylcholinesterase inhibition by fasciculin: A 5-ns molecular dynamics simulation. J. Am. Chem. Soc., 2002, 124, 6153-6161. (Pubitemid 34552859)
94. Bui, J.M.; Henchman, R.H.; McCammon, J.A. The dynamics of ligand barrier crossing inside the acetylcholinesterase gorge. Biophys. J., 2003, 85, 2267-2272. (Pubitemid 37210777)
95. Cavalli, A.; Bottegoni, G.; Raco, C.; De Vivo, M.; Recanatini, M. A computational study of the binding of propidium to the peripheral anionic site of human acetylcholinesterase. J. Med. Chem., 2004, 47, 3991-3999. (Pubitemid 38970960)
96. Hurley, M.M.; Balboa, A.; Lushington, G.H.; Guo, J. Interactions of organophosphorus and related compounds with cholinesterases, a theoretical study. Chem. Biol. Interact., 2005, 157, 321-325. (Pubitemid 41757668)
97. Henchman, R.H.; Tai, K.; Shen, T.; McCammon, JA. Properties of water molecules in the active site gorge of acetylcholinesterase from computer simulation. Biophys J., 2002, 82, 2671-2682. (Pubitemid 34441305)
98. Shi, J.; Tai, K.; McCammon, J.A.; Taylor, P.; Johnson, D.A. Nanosecond dynamics of the mouse acetylcholinesterase cys69-cys96 omega loop. J. Biol. Chem., 2003, 278, 30905-30911. (Pubitemid 36994602)
99. Xu, Y.; Shen, J.; Luo, X.; Silman, I.; Sussman, J.L.; Chen, K.; Jiang, H. How does huperzine A enter and leave the binding gorge of acetylcholinesterase? Steered molecular dynamics simulations. J. Am. Chem. Soc., 2003, 125, 11340-11349. (Pubitemid 37108071)
100. Gao, D.; Zhan, C.G. Modeling evolution of hydrogen bonding and stabilization of transition states in the process of cocaine hydrolysis catalyzed by human butyrylcholinesterase. Proteins, 2006, 62, 99-110. (Pubitemid 43063008)
101. Cheng, Y.; Cheng, X.; Radić, Z.; McCammon, J.A. Acetylcholinesterase: Mechanisms of covalent inhibition of wild-type and H447I mutant determined by computational analyses. J. Am. Chem. Soc., 2007, 129, 6562-6570. (Pubitemid 46799354)
102. Wlodek, S.T.; Shen, T.; McCammon, J.A. Electrostatic steering of substrate to acetylcholinesterase: Analysis of field fluctuations. Biopolymers, 2000, 53, 265-271. (Pubitemid 30082313)
103. Van Belle, D.; De Maria, L.; Iurcu, G.; Wodak, S.J. Pathways of ligand clearance in acetylcholinesterase by multiple copy sampling. J. Mol. Biol. 2000, 298, 705-726.
104. Petraglio, G.; Bartolini, M.; Branduardi, D.; Andrisano, V.; Recanatini, M.; Gervasio, F.L.; Cavalli, A.; Parrinello, M. The role of Li+, Na+, and K+ in the ligand binding inside the human acetylcholinesterase gorge. Proteins, 2008, 70, 779-785. (Pubitemid 351161938)
105. Gorfe, A.A.; Chang, C.E.; Ivanov, I.; McCammon, J.A. Dynamics of the acetylcholinesterase tetramer. Biophys. J., 2008, 94, 1144-1154.
106. Srain, B.M.; Rudolph, A.J. Alteration of acetylcholinesterase activity in Semele solida (MOLLUSCA: SEMELIDAE) as a biochemical response to coastal anthropogenic impact. J. Environ. Sci. Health B., 2008, 43, 75-80.
107. Xu, Y.; Colletier, J.P.; Jiang, H.; Silman, I.; Sussman, J.L.; Weik, M. Induced- fit or preexisting equilibrium dynamics? Lessons from protein crystallography and MD simulations on acetylcholinesterase and implications for structure-based drug design. Protein Sci., 2008, 17, 601-605. (Pubitemid 351480853)
108. Fan, F.; You, Z.; Li, Z.; Cheng, J.; Tang, Y.; Tang, Z. A butterfly effect: Highly insecticidal resistance caused by only a conservative residue mutated of drosophila melanogaster acetylcholinesterase. J. Mol. Model., 2009, 15, 1229-1236.
109. Guevara-Salazar, J.A.; Espinoza-Fonseca, M.; Beltrán, H.I.; Correa-Basurto, J.; Quintana-Zavala, D.; Trujillo-Ferrara, J.G. The electronic influence on the active site-directed inhibition of acetylcholinesterase by N-aryl-substituted succinimides. J. Mex. Chem. Soc., 2007, 51, 173-177.
110. Majumdar, D.; Roszak, S.; Leszczynski, J. Probing the acetylcholinesterase inhibition of sarin: A comparative interaction study of the inhibitor and acetylcholine with a model enzyme cavity. J. Phys. Chem. B., 2006, 110, 13597-13607. (Pubitemid 44115599)
111. Senapati, S.; Cheng, Y.; McCammon, J.A. In-situ synthesis of a tacrinetriazole- based inhibitor of acetylcholinesterase: Configurational selection imposed by steric interactions. J. Med. Chem., 2006, 49, 6222-6230. (Pubitemid 44595199)
112. Mastrantonio, G.; Mack, H.G.; Della Védova, C.O. Interpretation of the mechanism of acetylcholinesterase inhibition ability by organophosphorus compounds through a new conformational descriptor, an experimental and theoretical study. J. Mol. Model., 2008, 14, 813-821.
113. Nemukhin, A.V.; Lushchekina, S.V.; Bochenkova, A.V.; Golubeva, A.A.; Varfolomeev, S.D. Characterization of a complete cycle of acetylcholinesterase catalysis by ab initio QM/MM modeling. J. Mol. Model., 2008, 14, 409-416.
114. Tachikawa, H.; Igarashi, M.; Nishihira, J.; Ishibashi, T. Ab initio model study on acetylcholinesterase catalysis: Potential energy surfaces of the proton transfer reactions. J. Photochem. Photobiol. B., 2005, 79, 11-23. (Pubitemid 40425342)
115. Zhang, Y.; Kua, J.; McCammon, J.A. Role of the catalytic triad and oxyanion hole in acetylcholinesterase catalysis: An ab initio QM/MM study. J. Am. Chem. Soc. 2002, 124, 10572-10577. (Pubitemid 34977409)
116. Lushington, G.H.; Guo, J.; Hurley, M.M. Acetylcholinesterase: Molecular modeling with the whole toolkit. Curr. Top Med. Chem., 2006, 6, 57-73.
117. Vellom, D.C.; Radic, Z.; Li, Y.; Pickering, N.A.; Camp, S.; Taylor, P. Amino acid residues controlling acetylcholinesterase and butyrylcholinesterase specificity. Biochemistry, 1993, 32, 12-17. (Pubitemid 23033314)
118. Recanatini, M.; Cavalli, A.; Belluti, F.; Piazzi, L.; Rampa, A.; Bisi, A.; Gobbi, S.; Valeti, P.; Andrisano, V.; Bartolini, M.; Cavrini, V. SAR of 9- amino-1,2,3,4-tetrahydroacridine-based acetylcholinesterase inhibitors: Synthesis, enzyme inhibitory activity, QSAR, and structure-based CoMFA of tacrine analogues. J. Med. Chem., 2000, 43, 2007-2018. (Pubitemid 30340940)
119. Sippl, W.; Contreras, J.M.; Parrot, I.; Rival, Y.M.; Wermuth, C.G. Structurebased 3D QSAR and design of novel acetylcholinesterase inhibitors. J. Comput. Aided Mol. Des. 2001, 15, 395-410. (Pubitemid 32454468)
120. El-Yazal, J.; Rao, S.N.; Mehl, A.; Sclikker Jr., W. Prediction of organophosphorus acetylcholinesterase inhibition using three-dimensional quantitative structure-activity relationship (3D-QSAR) methods. Toxicol. Sci., 2001, 63, 223-232. (Pubitemid 32982796)
121. Zaheer-ul-Haq; Wellenzohn, B.; Tonmunphean, S.; Khalid, A.; Choudhary, M.I.; Rode, B.M. 3D-QSAR Studies on natural acetylcholinesterase inhibitors of Sarcococca saligna by comparative molecular field analysis (CoMFA). Bioorg. Med. Chem. Lett. 2003, 13, 4375-4380. (Pubitemid 37490821)
122. Chandrasekaran, V.; McGaughey, G.B.; Cavallite, C.J.; Bowen, J. Threedimensional quantitative structure-activity relationship (3D-QSAR) analyses of choline acetyltransferase inhibitors. J. Mol. Graph. Model., 2004, 23, 69-76. (Pubitemid 39141247)
123. Cho, S.J.; Garsia, M.L.; Bier, J.; Tropsha, A. Structure-based alignment and comparative molecular field analysis of acetylcholinesterase inhibitors. J. Med. Chem., 1996, 39, 5064-5071. (Pubitemid 27008953)
124. Bernard, P.; Kireev, D.B.; Chretien, J.R.; Fortier, P.L.; Coppet, L. Automated docking of 82 N-benzylpiperidine derivatives to mouse acetylcholinesterase and comparative molecular field analysis with 'natural' alignment. J. Comput. Aided Mol. Des. 1999, 13, 355-371. (Pubitemid 29337417)
125. Su, C.T.; Lien, E.J. QSAR of acetylchol inesterase inhibitors: A reexamination of the role of charge-transfer. Res. Commun. Chem. Pathol. Pharmacol., 1980, 29, 403-415. (Pubitemid 10055742)
126. Cardozo, M.G.; Iimura, Y.; Sugimoto, H.; Yamanishi, Y.; Hopfinger, A.J. QSAR analyses of the substituted indanone and benzylpiperidine rings of a series of indanone-benzylpiperidine inhibitors of acetylcholinesterase. J. Med. Chem., 1992, 35, 584-589.
127. Tong, W.; Collantes, E.R.; Chen, Y.; Welsh, W.J. A comparative molecular field analysis study of N-benzylpiperidines as acetylcholinesterase inhibitors. J. Med. Chem., 1996, 39, 380-387. (Pubitemid 26041451)
128. Hasegawa, K.; Kimura, T.; Funatsu, K. GA strategy for variable selection in QSAR studies: Application of GA-based region selection to a 3D-QSAR study of acetylcholinesterase inhibitors. J. Chem. Inf. Comput. Sci., 1999, 39, 112-120. (Pubitemid 129676566)
129. Akula, N.; Lecanu, L.; Greesonc, J.; Papadopoulos, V. 3D QSAR studies of AChE inhibitors based on molecular docking scores and CoMFA. Bioorg. Med. Chem. Lett., 2006, 16, 6277-6280. (Pubitemid 44709910)
130. Fernández, M.; Carreiras, M.C.; Marco, J.L.; Caballero, J. Modeling of acetylcholinesterase inhibition by tacrine analogues using Bayesianregularized Genetic Neural Networks and ensemble averaging. J. Enz. Inhib. Med. Chem., 2006, 21, 647-661. (Pubitemid 44970953)
131. Fernández, M.; Caballero, J. Ensembles of bayesian-regularized genetic neural networks for modeling of acetylcholinesterase inhibition by huprines. Chem. Biol. Drug. Des., 2006, 68, 201-212. (Pubitemid 44760245)
132. Elgorashi, E.E.; Malan, S.F.; Stafford, G.I.; van Staden, J. Quantitative structure-activity relationship studies on acetylcholinesterase enzyme inhibitory effects of Amaryllidaceae alkaloids. S. Afr. J. Bot., 2006, 72, 224-231. (Pubitemid 43983072)
133. Jung, M.; Tak, J.; Lee, Y.; Jung, Y. Quantitative structure-activity relationship (QSAR) of tacrine derivatives against acetylcholinesterase (AChE) activity using variable selections. Bioorg. Med. Chem. Lett., 2007, 17, 1082-1090. (Pubitemid 46177603)
134. Arning, J.; Stolte, S.; Böschen, A.; Stock, F.; Pitner, W.R.; Welz-Biermann, U.; Jastorff, B.; Rankea, J. Qualitative and quantitative structure activity relationships for the inhibitory effects of cationic head groups, functionalised side chains and anions of ionic liquids on acetylcholinesterase. Green Chem., 2008, 10, 47-58.
135. Liu, A.; Guang, H.; Zhu, L.; Du, G.; Lee, S.M.; Wang, Y. 3D-QSAR analysis of a new type of acetylcholinesterase inhibitors. Sci. China C. Life Sci., 2007, 50, 726-730 (Pubitemid 350172387)
136. Roy, K.K.; Dixit, A.; Saxena, A.K. An investigation of structurally diverse carbamates for acetylcholinesterase (AChE) inhibition using 3D-QSAR analysis. J. Mol. Graph. Model., 2008, 27, 197-208
137. Chekmarev, D.; Kholodovych, V.; Kortagere, S.; Welsh, W.J.; Ekins, S. Predicting inhibitors of acetylcholinesterase by regression and classification machine learning approaches with combinations of molecular descriptors. Pharm. Res., 2009, 26, 2216-2224.
138. Ognichenko, L.N.; Kuz-min, V.E.; Artemenko, A.G. New structural descriptors of molecules on the basis of symbiosis of the informational field model and simplex representation of molecular structure. QSAR Comb. Sci., 2009, 28, 939-945.
139. Saracoglu, M.; Kandemirli, F. The structure-AChE inhibitory activity relationships study in a series of pyridazine analogues. Med. Chem., 2009, 5, 325-335.
140. Kuz'min V. E., Muratov E. N., Artemenko A. G. , Varlamova E. V. , Gorb L., Wang J., and Leszczynski J. Consensus QSAR modeling of phosphorcontaining chiral AchE inhibitors. QSAR Comb. Sci., 2009, 28, 664-677.
141. Castilho, M.S.; Guido, R.V.C.; Andricopulo, A.D. Classical and hologram QSAR studies on a series of tacrine derivatives as butyrylcholinesterase inhibitors. Lett Drug Des. Disc., 2007, 4, 106-113. (Pubitemid 46121456)
142. Solomon, K.A.; Sundararajan, S.; Abirami, V. QSAR studies on N-aryl derivative activity towards Alzheimer's disease. Molecules, 2009, 14, 1448-1455.