Synthesis and biological evaluation of novel flavonoid derivatives as dual binding acetylcholinesterase inhibitors

Journal of Enzyme Inhibition and Medicinal Chemistry

Volumn 24, Issue 2, 2009, Pages 372-380

  Shen, Yanhong ^a,b   Zhang, Jing ^a   Sheng, Rong ^a   Dong, Xiaowu ^a   He, Qiaojun ^a   Yang, Bo ^a   Hu, Yongzhou ^a  

^a ZHEJIANG UNIVERSITY   (China)

^b ANYANG INSTITUTE OF TECHNOLOGY   (China)

Author keywords

Acetylcholinesterase; Alzheimer's disease; Benzylpiperidine; Flavonoids; Inhibitors

Indexed keywords

2 [3 (1 BENZYLPIPERIDIN 4 YLOXY)PHENYL] 6,7 DIMETHOXY 4H CHROMEN 4 ONE; 2 [3 (1 BENZYLPIPERIDIN 4 YLOXY)PHENYL] 6,7 DIMETHOXYCHROMAN 4 ONE; 2 [3 [(1 BENZYLPIPERIDIN 4 YL)METHOXY]PHENYL] 6,7 DIMETHOXY 4H CHROMEN 4 ONE; 2 [3 [(1 BENZYLPIPERIDIN 4 YL)METHOXY]PHENYL] 6,7 DIMETHOXYCHROMAN 4 ONE; 2 [4 (1 BENZYLPIPERIDIN 4 YLOXY)PHENYL] 6,7 DIMETHOXY 4H CHROMEN 4 ONE; 2 [4 (1 BENZYLPIPERIDIN 4 YLOXY)PHENYL] 6,7 DIMETHOXYCHROMAN 4 ONE; 2 [4 [(1 BENZYLPIPERIDIN 4 YL)METHOXY]PHENYL] 6,7 DIMETHOXY 4H CHROMEN 4 ONE; 2 [4 [(1 BENZYLPIPERIDIN 4 YL)METHOXY]PHENYL] 6,7 DIMETHOXYCHROMAN 4 ONE; 3 (1 BENZYLPIPERIDIN 4 YLOXY)BENZALDEHYDE; 3 [(1 BENZYLPIPERIDIN 4 YL)METHOXY]BENZALDEHYDE; 3 [3 (1 BENZYLPIPERIDIN 4 YLOXY)PHENYL] 1 (2 HYDROXY 4,5 DIMETHOXYPHENYL)PROP 2 EN 1 ONE; 3 [3 (1 BENZYLPIPERIDIN 4 YLOXY)PHENYL] 6,7 DIMETHOXY 4H CHROMEN 4 ONE; 3 [3 [(1 BENZYLPIPERIDIN 4 YL)METHOXY]PHENYL] 1 (2 HYDROXY 4,5 DIMETHOXYPHENYL)PROP 2 EN 1 ONE; 3 [3 [(1 BENZYLPIPERIDIN 4 YL)METHOXY]PHENYL] 6,7 DIMETHOXY 4H CHROMEN 4 ONE; 3 [4 (1 BENZYLPIPERIDIN 4 YLOXY)PHENYL] 1 (2 HYDROXY 4,5 DIMETHOXYPHENYL)PROP 2 EN 1 ONE; 3 [4 (1 BENZYLPIPERIDIN 4 YLOXY)PHENYL] 6,7 DIMETHOXY 4H CHROMEN 4 ONE; 3 [4 [(1 BENZYLPIPERIDIN 4 YL)METHOXY]PHENYL] 1 (2 HYDROXY 4,5 DIMETHOXYPHENYL)PROP 2 EN 1 ONE; 3 [4 [(1 BENZYLPIPERIDIN 4 YL)METHOXY]PHENYL] 6,7 DIMETHOXY 4H CHROMEN 4 ONE; 4 (1 BENZYLPIPERIDIN 4 YLOXY)BENZALDEHYDE; 4 [(1 BENZYLPIPERIDIN 4 YL)METHOXY]BENZALDEHYDE; ACETYLCHOLINESTERASE; CHOLINESTERASE; CHOLINESTERASE INHIBITOR; DONEPEZIL; FLAVONOID; ISOFLAVONE; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; ARTICLE; DRUG BINDING SITE; DRUG DESIGN; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG SCREENING; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME ACTIVE SITE; ENZYME ASSAY; ENZYME INHIBITION; IC 50; MOLECULAR DOCKING; MOLECULAR INTERACTION; MOLECULAR MODEL; NONHUMAN; PRIORITY JOURNAL; RAT; STRUCTURE ACTIVITY RELATION; BINDING SITE; CHEMICAL STRUCTURE; COMPUTER SIMULATION; KINETICS; METABOLISM; SYNTHESIS; X RAY CRYSTALLOGRAPHY;

ACETYLCHOLINESTERASE; BINDING SITES; CHOLINESTERASE INHIBITORS; COMPUTER SIMULATION; CRYSTALLOGRAPHY, X-RAY; FLAVONOIDS; INHIBITORY CONCENTRATION 50; KINETICS; MODELS, MOLECULAR; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 68049112477     PISSN: 14756366     EISSN: 14756374     Source Type: Journal    
DOI: 10.1080/14756360802187885     Document Type: Article

References (22)

1. Bachurin SO. Medicinal chemistry approaches for the treatment and prevention of Alzheimer's disease. Med Res Rev 2003;23(1):48-88.
2. Tariot P, Federoff H. Current treatment for Alzheimer disease and future prospects. Alzheimer Dis Assoc Disord 2003;17:105-113.
3. Giacobini E. Cholinesterase inhibitors: New roles and therapeutic alternatives. Pharmacol Res 2004;50(4):433-440.
4. Evans J, Wilcock G, Birks J. Evidence-based pharmacotherapy of Alzheimer's disease. Int J Neuropsychopharmacol 2004; 7(3):351-369.
5. Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer's disease: Progress and problems on the road to therapeutics. Science 2002;297(5580):353- 356.
6. De Ferrari GV, Canales MA, Shin I, Weiner LM, Silman I, Inestrosa NC. A structural motif of acetylcholinesterase that promotes amyloid beta-peptide fibril formation. Biochemistry 2001;40(35):10447-10457.
7. AlonsoD,Dorronsoro I,Rubio L,MunozP,Garcia-PalomeroE, Del Monte M, Bidon-Chanal A, Orozco M, Luque FJ, Castro A, Medina M, Martinez A. Donepezil-tacrine hybrid related derivatives as new dual binding site inhibitors of AChE. Bioorg Med Chem 2005;13(24):6588-6597.
8. Piazzi L, Belluti F, Bisi A, Gobbi S, Rizzo S, Bartolini M, Andrisano V, Recanatini M, Rampa A. Cholinesterase inhibitors: SAR and enzyme inhibitory activity of 3-[omega- (benzylmethylamino)alkoxy] xanthen-9-ones. Bioorg Med Chem 2007;15(1):575-585.
9. Wang CN, Chi CW, Lin YL, Chen CF, Shiao YJ. The neuroprotective effects of phytoestrogens on amyloid beta protein-induced toxicity are mediated by abrogating the activation of caspase cascade in rat cortical neurons. J Biol Chem 2001;276:5287-5295.
10. Kim H, Park BS, Lee KG, Choi CY, Jang SS, KimYH, Lee SE. Effects of naturally occurring compounds on fibril formation and oxidative stress of b-amyloid. J Agric Food Chem 2005; 53(22):8537-8541.
11. Zhu J, Choi R, Chu G, Cheung A, Gao Q, Li J, Jiang ZY, Dong T, Tsim K. Flavonoids possess neuroprotective effects on cultured pheochromocytoma PC12 cells: A comparison of different flavonoids in activating estrogenic effect and in preventing b-amyloid-induced cell death. J Agric Food Chem 2007;55(6):2438-2445.
12. Kryger G, Silman I, Sussman JL. Three-dimensional structure of a complex of E2020 with acetylcholinesterase from Torpedo Californica. J Physiol (Paris) 1998;92:191-194.
13. Mitsunobu O. The use of diethyl azodicarboxylate and triphenylphosphine in synthesis and transformation of natural products. Synthesis 1981;1:1-28.
14. Shaw J, Lee AR, Huang WH. Methods of synthesizing flavonoids and chalcones, US 2004242907.
15. Xiao L, Tan WF, Li YL. First total synthesis of (^)- kenusanone B. Synth Commun 1998;28(15):2861-2869.
16. Mavel S, Dikic B, Palakas S. Synthesis and biological evaluation of a series of flavone derivatives as potential radioligands for imaging the multidrug resistance-associated protein 1 (ABCC1/MRP1). Bioorg Med Chem 2006;14(5): 1599-1607.
17. Masao T, Hironari W, Yasuhiko K. Regioselective synthesis of 6-alkyl- and 6-prenylpolyhydroxyisoflavones and 6-alkylcoumaronochromone derivatives. Chem PharmBull 2004;52(11): 1285-1289.
18. Yasuhiko K, Masashi M, Takanori T. Synthesis of isoflavones from 20-hydroxy- chalcones using poly[4-(diacetoxy)iodo]styrene or related hypervalent iodine reagent. Synthesis 2002;17: 2490-2496.
19. Cousins MS, Carriero DL, Salamone JD. Tremulous jaw movements induced by the acetylcholinesterase inhibitor tacrine: Effects of antiparkinsonian drugs. Eur J Pharmacol 1997;322:137-145.
20. Ellman GL, Courtney KD, Andres V, Jr., Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 1961;7:88-95.
21. Cheng DH, Tang XC. Comparative studies of huperzine A, E2020, and tacrine on behavior and cholinesterase activities. Pharmacol Biochem Behav 1998;60(2):377-386.
22. SYBYL 6.9 molecular modeling program., Tripos Associates.