Nature as a source of metabolites with cholinesterase-inhibitory activity: An approach to Alzheimer's disease treatment

Journal of Pharmacy and Pharmacology

Volumn 65, Issue 12, 2013, Pages 1681-1700

  Pinho, Brígida R ^a   Ferreres, Federico ^b   Valentão, Patrícia ^a   Andrade, Paula B ^a  

^a UNIVERSITY OF PORTO   (Portugal)

^b RESEARCH GROUP ON QUALITY   (Spain)

Author keywords

biomedicinal chemistry; clinical efficacy of natural products; drugs from natural sources; structure activity relationships

Indexed keywords

3 CARENE; ACETYLCHOLINESTERASE; ALPHA VINIFERIN; APIGENIN; ARISUGACIN A; ARISUGACIN B; BERBERINE; CHOLINESTERASE; CHOLINESTERASE INHIBITOR; COUMARIN DERIVATIVE; FISETIN; FLAVONE DERIVATIVE; FLAVONOID; GALANGIN; GALANTAMINE; ISOFLAVONE DERIVATIVE; KAEMPFEROL; LUTEOLIN; NATURAL PRODUCT; PHYSOSTIGMINE; QUERCETIN; QUINONE DERIVATIVE; RIVASTIGMINE; SARGAQUINOIC ACID; STILBENE DERIVATIVE; TAMARIXETIN; TERPENE; TERRITREM B; UNCLASSIFIED DRUG; UNINDEXED DRUG; XANTHONE DERIVATIVE;

ALZHEIMER DISEASE; ANTICHOLINESTERASES ACTIVITY; CONCENTRATION RESPONSE; DRUG ACTIVITY; DRUG POTENCY; DRUG STRUCTURE; GALANTHUS; GALANTHUS NIVALIS; HUMAN; METABOLITE; NONHUMAN; REVIEW;

BIOMEDICINAL CHEMISTRY; CLINICAL EFFICACY OF NATURAL PRODUCTS; DRUGS FROM NATURAL SOURCES; STRUCTURE/ACTIVITY RELATIONSHIPS;

ALKALOIDS; ALZHEIMER DISEASE; BIOLOGICAL PRODUCTS; CHOLINESTERASE INHIBITORS; CHOLINESTERASES; COUMARINS; FLAVONOIDS; HUMANS; QUINONES; STILBENES; XANTHONES;

EID: 84887889052     PISSN: 00223573     EISSN: 20427158     Source Type: Journal    
DOI: 10.1111/jphp.12081     Document Type: Review

References (140)

1. Uttara B, et al. Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr Neuropharmacol 2009; 7: 65-74.
2. Jucker M, Walker LC,. Pathogenic protein seeding in Alzheimer disease and other neurodegenerative disorders. Ann Neurol 2011; 70: 532-540.
3. Alzheimer's Association. 2012 Alzheimer's disease facts and figures. Alzheimers Dement 2012; 8: 131-168.
4. Mattson MP,. Pathways towards and away from Alzheimer's disease. Nature 2004; 430: 631-639.
5. Reddy PH,. Abnormal tau, mitochondrial dysfunction, impaired axonal transport of mitochondria, and synaptic deprivation in Alzheimer's disease. Brain Res 2011; 1415: 136-148.
6. Mao P, Reddy PH,. Aging and amyloid β-induced oxidative DNA damage and mitochondrial dysfunction in Alzheimer's disease: implications for early intervention and therapeutics. Biochim Biophys Acta 2011; 1812: 1359-1370.
7. Reitz C, et al. Epidemiology of Alzheimer disease. Nat Rev Neurol 2011; 7: 137-152.
8. O'Brien RJ, Wong PC,. Amyloid precursor protein processing and Alzheimer's disease. Annu Rev Neurosci 2011; 34: 185-204.
9. Szymanski M, et al. Alzheimer's risk variants in the clusterin gene are associated with alternative splicing. Transl Psychiatry 2011; 1: e18. doi: 10.1038/tp.2011.17.
10. Lee JH, et al. The neuronal sortilin-related receptor gene SORL1 and late-onset Alzheimer's disease. Curr Neurol Neurosci Rep 2008; 8: 384-391.
11. Assal F, Cummings JL,. Neuropsychiatric symptoms in the dementias. Curr Opin Neurol 2002; 15: 445-450.
12. Perrin RJ, et al. Multimodal techniques for diagnosis and prognosis of Alzheimer's disease. Nature 2009; 461: 916-922.
13. Blennow K, et al. Alzheimer's disease. Lancet 2006; 368: 387-403.
14. Zhang L, et al. Current neuroimaging techniques in Alzheimer's disease and applications in animal models. Am J Nucl Med Mol Imaging 2012; 2: 386-404.
15. Selkoe DJ,. Alzheimer's disease: genes, proteins, and therapy. Physiol Rev 2001; 81: 741-766.
16. Hardy J, Selkoe DJ,. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 2002; 297: 353-356.
17. Scarpini E, et al. Treatment of Alzheimer's disease: current status and new perspectives. Lancet Neurol 2003; 2: 539-547.
18. Schliebs R, Arendt T,. The cholinergic system in aging and neuronal degeneration. Behav Brain Res 2011; 221: 555-563.
19. Beatty WW, et al. Patterns of memory failure after scopolamine treatment: implications for cholinergic hypotheses of dementia. Behav Neural Biol 1986; 45: 196-211.
20. Sherman SJ, et al. Scopolamine impairs human recognition memory: data and modeling. Behav Neurosci 2003; 117: 526-539.
21. Fukami T, Yokoi T,. The emerging role of human esterases. Drug Metab Pharmacokinet 2012; 27: 466-477.
22. Darvesh S, et al. Neurobiology of butyrylcholinesterase. Nat Rev Neurosci 2003; 4: 131-138.
23. Jbilo O, et al. Tissue distribution of human acetylcholinesterase and butyrylcholinesterase messenger RNA. Toxicon 1994; 32: 1445-1457.
24. Kasa P, et al. The cholinergic system in Alzheimer's disease. Prog Neurobiol 1997; 52: 511-535.
25. Houghton PJ, et al. Acetylcholinesterase inhibitors from plants and fungi. Nat Prod Rep 2006; 23: 181-199.
26. Perry EK, et al. Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Br Med J 1978; 2: 1457-1459.
27. Davies P, Maloney AJ,. Selective loss of central cholinergic neurons in Alzheimer's disease. Lancet 1976; 2: 1403.
28. Xie W, et al. Postnatal developmental delay and supersensitivity to organophosphate in gene-targeted mice lacking acetylcholinesterase. J Pharmacol Exp Ther 2000; 293: 896-902.
29. Fukuchi K, et al. Amelioration of amyloid load by anti-Aβ single-chain antibody in Alzheimer mouse model. Biochem Biophys Res Commun 2006; 344: 79-86.
30. Ibach B, Haen E,. Acetylcholinesterase inhibition in Alzheimer's disease. Curr Pharm Des 2004; 10: 231-251.
31. Kinghorn AD, et al. The relevance of higher plants in lead compound discovery programs. J Nat Prod 2011; 74: 1539-1555.
32. Kennedy DO, Wightman EL,. Herbal extracts and phytochemicals: plant secondary metabolites and the enhancement of human brain function. Adv Nutr 2011; 2: 32-50.
33. Khalid A, et al. Kinetics and structure-activity relationship studies on pregnane-type steroidal alkaloids that inhibit cholinesterases. Bioorg Med Chem 2004; 12: 1995-2003.
34. Jung HA, et al. Anti-Alzheimer and antioxidant activities of Coptidis Rhizoma alkaloids. Biol Pharm Bull 2009; 32: 1433-1438.
35. McGehee DS, et al. Cholinesterase inhibition by potato glycoalkaloids slows mivacurium metabolism. Anesthesiology 2000; 93: 510-519.
36. 8- bisnorcymserine. Tetrahedron Lett 2000; 41: 4861-4864.
37. Pejchal V, et al. 1,3-Substituted imidazolidine-2,4,5-triones: synthesis and inhibition of cholinergic enzymes. Molecules 2011; 16: 7565-7582.
38. Bai DL, et al. Huperzine A, a potential therapeutic agent for treatment of Alzheimer's disease. Curr Med Chem 2000; 7: 355-374.
39. Geissler T, et al. Acetylcholinesterase inhibitors from the toadstool Cortinarius infractus. Bioorg Med Chem 2010; 18: 2173-2177.
40. Choudhary MI, et al. Juliflorine: a potent natural peripheral anionic-site-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.
41. Kishibayashi N, et al. Inhibitory effects of KW-5092, a novel gastroprokinetic agent, on the activity of acetylcholinesterase in guinea pig ileum. Jpn J Pharmacol 1994; 66: 397-403.
42. Nukoolkarn VS, et al. Petrosamine, a potent anticholinesterase pyridoacridine alkaloid from a Thai marine sponge Petrosia n. sp. Bioorg Med Chem 2008; 16: 6560-6567.
43. Thomsen T, et al. Inhibition of acetylcholinesterase activity in human brain tissue and erythrocytes by galanthamine, physostigmine and tacrine. Eur J Clin Chem Clin Biochem 1991; 29: 487-492.
44. Iijima S, et al. The long-acting cholinesterase inhibitor heptyl-physostigmine attenuates the scopolamine-induced learning impairment of rats in a 14-unit T-maze. Neurosci Lett 1992; 144: 79-83.
45. Wilson BW, et al. Actions of pyridostigmine and organophosphate agents on chick cells, mice, and chickens. Drug Chem Toxicol 2002; 25: 131-139.
46. Cerasoli DM, et al. In vitro and in vivo characterization of recombinant human butyrylcholinesterase (Protexia) as a potential nerve agent bioscavenger. Chem Biol Interact 2005; 157-158: 363-365.
47. Seto Y, Shinohara T,. Structure-activity relationship of reversible cholinesterase inhibitors including paraquat. Arch Toxicol 1988; 62: 37-40.
48. Kang SY, et al. Coumarins isolated from Angelica gigas inhibit acetylcholinesterase: structure-activity relationships. J Nat Prod 2001; 64: 683-685.
49. Wszelaki N, et al. Bioactivity-guided fractionation for the butyrylcholinesterase inhibitory activity of furanocoumarins from Angelica archangelica L. roots and fruits. J Agric Food Chem 2011; 59: 9186-9193.
50. Miyazawa M, et al. Insecticidal effect of phthalides and furanocoumarins from Angelica acutiloba against Drosophila melanogaster. J Agric Food Chem 2004; 52: 4401-4405.
51. Kim JK, et al. Effects of methoxsalen from Poncirus trifoliata on acetylcholinesterase and trimethyltin-induced learning and memory impairment. Biosci Biotechnol Biochem 2011; 75: 1984-1989.
52. Lee JH, et al. Acetylcholinesterase inhibitors from the twigs of Vaccinium oldhami Miquel. Arch Pharm Res 2004; 27: 53-56.
53. Guo AJ, et al. Galangin, a flavonol derived from Rhizoma Alpiniae Officinarum, inhibits acetylcholinesterase activity in vitro. Chem Biol Interact 2010; 187: 246-248.
54. Min BS, et al. Cholinesterase inhibitors from Cleistocalyx operculatus buds. Arch Pharm Res 2010; 33: 1665-1670.
55. Noor A, et al. Leufolins A and B, potent butyrylcholinesterase-inhibiting flavonoid glucosides from Leucas urticifolia. Molecules 2007; 12: 1447-1454.
56. Cho JK, et al. Cholinestrase inhibitory effects of geranylated flavonoids from Paulownia tomentosa fruits. Bioorg Med Chem 2012; 20: 2595-2602.
57. Orhan I, et al. Cholinesterase inhibitory effects of the extracts and compounds of Maclura pomifera (Rafin.) Schneider. Food Chem Toxicol 2009; 47: 1747-1751.
58. Khan MT, et al. Cholinesterase inhibitory activities of some flavonoid derivatives and chosen xanthone and their molecular docking studies. Chem Biol Interact 2009; 181: 383-389.
59. Öztürk M, et al. Antioxidant and anticholinesterase active constituents from Micromeria cilicica by radical-scavenging activity-guided fractionation. Food Chem 2011; 126: 31-38.
60. Changwong N, et al. Acetyl- and butyryl-cholinesterase inhibitory activities of mansorins and mansonones. Phytother Res 2012; 26: 392-396.
61. Choi BW, et al. Anticholinesterase activity of plastoquinones from Sargassum sagamianum: lead compounds for Alzheimer's disease therapy. Phytother Res 2007; 21: 423-426.
62. Sung SH, et al. (+)-α-Viniferin, a stilbene trimer from Caragana chamlague, inhibits acetylcholinesterase. Biol Pharm Bull 2002; 25: 125-127.
63. Sermboonpaisarn T, Sawasdee P,. Potent and selective butyrylcholinesterase inhibitors from Ficus foveolata. Fitoterapia 2012; 83: 780-784.
64. Perry NS, et al. In vitro inhibition of human erythrocyte acetylcholinesterase by Salvia lavandulaefolia essential oil and constituent terpenes. J Pharm Pharmacol 2000; 52: 895-902.
65. Miyazawa M, Yamafuji C,. Inhibition of acetylcholinesterase activity by bicyclic monoterpenoids. J Agric Food Chem 2005; 53: 1765-1768.
66. Savelev SU, et al. Butyryl- and acetyl-cholinesterase inhibitory activities in essential oils of Salvia species and their constituents. Phytother Res 2004; 18: 315-324.
67. Wong KK, et al. Interaction study of two diterpenes, cryptotanshinone and dihydrotanshinone, to human acetylcholinesterase and butyrylcholinesterase by molecular docking and kinetic analysis. Chem Biol Interact 2010; 187: 335-339.
68. Hung TM, et al. Labdane-type diterpenoids from Leonurus heterophyllus and their cholinesterase inhibitory activity. Phytother Res 2011; 25: 611-614.
69. Ahmad VU, et al. Three new cholinesterase-inhibiting cis-clerodane diterpenoids from Otostegia limbata. Chem Pharm Bull 2005; 53: 378-381.
70. Kaufmann D, et al. Myrtenal inhibits acetylcholinesterase, a known Alzheimer target. J Pharm Pharmacol 2011; 63: 1368-1371.
71. Koay YC, et al. Chemical constituents and biological activities of Strobilanthes crispus L. Rec Nat Prod 2013; 7: 59-64.
72. Lenta BN, et al. Leishmanicidal and cholinesterase inhibiting activities of phenolic compounds from Allanblackia monticola and Symphonia globulifera. Molecules 2007; 12: 1548-1557.
73. Urbain A, et al. Xanthones from Gentianella amarella ssp. acuta with acetylcholinesterase and monoamine oxidase inhibitory activities. J Nat Prod 2008; 71: 895-897.
74. Al-Rashid ZF, Hsung RP,. (+)-Arisugacin A-computational evidence of a dual binding site covalent inhibitor of acetylcholinesterase. Bioorg Med Chem Lett 2011; 21: 2687-2691.
75. Kuno F, et al. Arisugacins A and B, novel and selective acetylcholinesterase inhibitors from Penicillium sp. FO-4259. II. Structure elucidation. J Antibiot (Tokyo) 1996; 49: 748-751.
76. Orhan IE, et al. An overview on natural cholinesterase inhibitors-a multi-targeted drug class-and their mass production. Mini Rev Med Chem 2011; 11: 836-842.
77. Mukherjee PK, et al. Lead finding for acetyl cholinesterase inhibitors from natural origin: structure activity relationship and scope. Mini Rev Med Chem 2011; 11: 247-262.
78. Barak D, et al. Accommodation of physostigmine and its analogues by acetylcholinesterase is dominated by hydrophobic interactions. Biochem J 2009; 417: 213-222.
79. Atack JR, et al. Comparative inhibitory effects of various physostigmine analogs against acetyl- and butyrylcholinesterases. J Pharmacol Exp Ther 1989; 249: 194-202.
80. Greig NH, et al. Selective butyrylcholinesterase inhibition elevates brain acetylcholine, augments learning and lowers Alzheimer β-amyloid peptide in rodent. Proc Natl Acad Sci U S A 2005; 102: 17213-17218.
81. Ji HF, Shen L,. Molecular basis of inhibitory activities of berberine against pathogenic enzymes in Alzheimer's disease. The Scientific World Journal 2012; 2012: 823201.
82. Panahi N, et al. Effects of berberine on β-secretase activity in a rabbit model of Alzheimer's disease. Arch Med Sci 2013; 9: 146-150.
83. Cousin X, et al. Cloning and expression of acetylcholinesterase from Bungarus fasciatus venom. A new type of cooh-terminal domain; involvement of a positively charged residue in the peripheral site. J Biol Chem 1996; 271: 15099-15108.
84. Wallin AK, et al. Galantamine treatment in Alzheimer's disease: response and long-term outcome in a routine clinical setting. Neuropsychiatr Dis Treat 2011; 7: 565-576.
85. Berkov S, et al. N-Alkylated galanthamine derivatives: potent acetylcholinesterase inhibitors from Leucojum aestivum. Bioorg Med Chem Lett 2008; 18: 2263-2266.
86. Lima JA, et al. Geissospermum vellosii stembark: anticholinesterase activity and improvement of scopolamine-induced memory deficits. Pharmacol Biochem Behav 2009; 92: 508-513.
87. Araujo JQ, et al. Docking of the alkaloid geissospermine into acetylcholinesterase: a natural scaffold targeting the treatment of Alzheimer's disease. J Mol Model 2011; 17: 1401-1412.
88. Passos CS, et al. Indole alkaloids of Psychotria as multifunctional cholinesterases and monoamine oxidases inhibitors. Phytochemistry 2013; 86: 8-20.
89. Zangara A,. The psychopharmacology of huperzine A: an alkaloid with cognitive enhancing and neuroprotective properties of interest in the treatment of Alzheimer's disease. Pharmacol Biochem Behav 2003; 75: 675-686.
90. Yang L, et al. Decreased accumulation of subcellular amyloid-β with improved mitochondrial function mediates the neuroprotective effect of huperzine A. J Alzheimers Dis 2012; 31: 131-142.
91. Wang Y, et al. Huperzine A alleviates synaptic deficits and modulates amyloidogenic and nonamyloidogenic pathways in APPswe/PS1dE9 transgenic mice. J Neurosci Res 2012; 90: 508-517.
92. Shi Q, et al. Huperzine A ameliorates cognitive deficits and oxidative stress in the hippocampus of rats exposed to acute hypobaric hypoxia. Neurochem Res 2012; 37: 2042-2052.
93. Zhang Y, et al. 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.
94. Rafii MS, et al. A phase II trial of huperzine A in mild to moderate Alzheimer disease. Neurology 2011; 76: 1389-1394.
95. Zaheer-ul-Haq, et al. 3D-QSAR studies on natural acetylcholinesterase inhibitors of Sarcococca saligna by comparative molecular field analysis (CoMFA). Bioorg Med Chem Lett 2003; 13: 4375-4380.
96. Elgorashi EE, et al. Acetylcholinesterase enzyme inhibitory effects of Amaryllidaceae alkaloids. Planta Med 2004; 70: 260-262.
97. Wang YH, et al. Synthesis and biological evaluation of lycorine derivatives as dual inhibitors of human acetylcholinesterase and butyrylcholinesterase. Chem Cent J 2012; 6: 96.
98. Halldorsdottir ES, et al. Acetylcholinesterase inhibitory activity of lycopodane-type alkaloids from the Icelandic Lycopodium annotinum ssp. alpestre. Phytochemistry 2010; 71: 149-157.
99. Adewusi EA, et al. Cytotoxicity and acetylcholinesterase inhibitory activity of an isolated crinine alkaloid from Boophane disticha (Amaryllidaceae). J Ethnopharmacol 2012; 143: 572-578.
100. Brunetton R,. Pharmacognosy: Phytochemistry Medicinal Plants, 2nd edn. Hampshire: Intercept Ltd., 1999.
101. Rollinger JM, et al. Acetylcholinesterase inhibitory activity of scopolin and scopoletin discovered by virtual screening of natural products. J Med Chem 2004; 47: 6248-6254.
102. Kim JK, et al. Inhibitory effect of Poncirus trifoliate on acetylcholinesterase and attenuating activity against trimethyltin-induced learning and memory impairment. Biosci Biotechnol Biochem 2009; 73: 1105-1112.
103. Senol FS, et al. An in vitro and in silico approach to cholinesterase inhibitory and antioxidant effects of the methanol extract, furanocoumarin fraction, and major coumarins of Angelica officinalis L. fruits. Phytochem Lett 2011; 4: 462-467.
104. Kang SY, et al. Decursin from Angelica gigas mitigates amnesia induced by scopolamine in mice. Neurobiol Learn Mem 2003; 79: 11-18.
105. Catto M, et al. Design, synthesis and biological evaluation of coumarin alkylamines as potent and selective dual binding site inhibitors of acetylcholinesterase. Bioorg Med Chem 2012; 21: 146-152.
106. Alipour M, et al. Novel coumarin derivatives bearing N-benzyl pyridinium moiety: potent and dual binding site acetylcholinesterase inhibitors. Bioorg Med Chem 2012; 20: 7214-7222.
107. Raza A, et al. Pharmacological evaluation and docking studies of 3-thiadiazolyl- and thioxo-1,2,4-triazolylcoumarin derivatives as cholinesterase inhibitors. ISRN Pharmacol 2012; 707932.
108. Rice-Evans CA, et al. Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radic Biol Med 1996; 20: 933-956.
109. Uriarte-Pueyo I, Calvo MI,. Flavonoids as acetylcholinesterase inhibitors. Curr Med Chem 2011; 18: 5289-5302.
110. Sheng R, et al. Design, synthesis and evaluation of flavonoid derivatives as potent AChE inhibitors. Bioorg Med Chem 2009; 17: 6692-6698.
111. Kim JY, et al. Isolation of cholinesterase-inhibiting flavonoids from Morus lhou. J Agric Food Chem 2011; 59: 4589-4596.
112. Jin CH, et al. Fustin flavonoid attenuates β-amyloid (1-42)-induced learning impairment. J Neurosci Res 2009; 87: 3658-3670.
113. Heo HJ, et al. Naringenin from Citrus junos has an inhibitory effect on acetylcholinesterase and a mitigating effect on amnesia. Dement Geriatr Cogn Disord 2004; 17: 151-157.
114. Katalinic̈ M, et al. Structural aspects of flavonoids as inhibitors of human butyrylcholinesterase. Eur J Med Chem 2010; 45: 186-192.
115. Sawasdee P, et al. Anticholinesterase activity of 7-methoxyflavones isolated from Kaempferia parviflora. Phytother Res 2009; 23: 1792-1794.
116. EL Omri A, et al. Luteolin enhances cholinergic activities in PC12 cells through ERK1/2 and PI3K/Akt pathways. Brain Res 2012; 1437: 16-25.
117. O'Brien PJ,. Molecular mechanisms of quinone cytotoxicity. Chem Biol Interact 1991; 80: 1-41.
118. Sperry J, et al. Pyranonaphthoquinone derivatives of eleutherin, ventiloquinone L, thysanone and nanaomycin A possessing a diverse topoisomerase II inhibition and cytotoxicity spectrum. Bioorg Med Chem 2009; 17: 7131-7137.
119. Chao SH, et al. Juglone, an inhibitor of the peptidyl-prolyl isomerase Pin1, also directly blocks transcription. Nucleic Acids Res 2001; 29: 767-773.
120. Klegeris A, et al. A possible interaction between acetylcholinesterase and dopamine molecules during autoxidation of the amine. Free Radic Biol Med 1995; 18: 223-230.
121. Vasudevan M, Parle M,. Pharmacological actions of Thespesia populnea relevant to Alzheimer's disease. Phytomedicine 2006; 13: 677-687.
122. Roupe KA, et al. Pharmacometrics of stilbenes: seguing towards the clinic. Curr Clin Pharmacol 2006; 1: 81-101.
123. Thanh VT, et al. Cytotoxic lignans from fruits of Cleistanthus indochinensis: synthesis of cleistantoxin derivatives. J Nat Prod 2012; 75: 1578-1583.
124. Aazza S, et al. Antioxidant and antiacetylcholinesterase activities of some commercial essential oils and their major compounds. Molecules 2011; 16: 7672-7690.
125. Picollo MI, et al. Anticholinesterase and pediculicidal activities of monoterpenoids. Fitoterapia 2008; 79: 271-278.
126. Savelev S, et al. Synergistic and antagonistic interactions of anticholinesterase terpenoids in Salvia lavandulaefolia essential oil. Pharmacol Biochem Behav 2003; 75: 661-668.
127. Ren Y, et al. Novel diterpenoid acetylcholinesterase inhibitors from Salvia miltiorhiza. Planta Med 2004; 70: 201-204.
128. Çulhaoǧlu B, et al. Bioactive constituents of Salvia chrysophylla Stapf. Nat Prod Res 2013; 27: 438-447.
129. Yilmaz A, et al. A novel isopimarane diterpenoid with acetylcholinesterase inhibitory activity from Nepeta sorgerae, an endemic species to the Nemrut Mountain. Nat Prod Commun 2012; 7: 693-696.
130. Chung YK, et al. Inhibitory effect of ursolic acid purified from Origanum majorana L on the acetylcholinesterase. Mol Cells 2001; 11: 137-143.
131. Fatima I, et al. New butyrylcholinesterase inhibitory steroid and peroxy acid from Leucas urticifolia. Arch Pharm Res 2008; 31: 999-1003.
132. Choudhary MI, et al. Withanolides, a new class of natural cholinesterase inhibitors with calcium antagonistic properties. Biochem Biophys Res Commun 2005; 334: 276-287.
133. Zarena AS, Udaya Sankar K,. Screening of xanthone from mangosteen (Garcinia mangostana L.) peels and their effect on cytochrome c reductase and phosphomolybdenum activity. J Nat Prod 2009; 2: 23-30.
134. Kang JJ, Fang HW,. Polycyclic aromatic hydrocarbons inhibit the activity of acetylcholinesterase purified from electric eel. Biochem Biophys Res Commun 1997; 238: 367-369.
135. Urbain AA, et al. Xanthones from Gentiana campestris as new acetylcholinesterase inhibitors. Planta Med 2004; 70: 1011-1014.
136. Chen JW, et al. Territrem B, a tremorgenic mycotoxin that inhibits acetylcholinesterase with a noncovalent yet irreversible binding mechanism. J Biol Chem 1999; 274: 34916-34923.
137. Chen JW, Ling KH,. Territrems: naturally occurring specific irreversible inhibitors of acetylcholinesterase. J Biomed Sci 1996; 3: 54-58.
138. Zhao Y, et al. Preparation of analogues of territrem B, a potent AChE inhibitor. Tetrahedron 2000; 56: 8901-8913.
139. Jiang X, et al. Design, synthesis, and biological evaluation of new territrem B analogues. Chem Biodivers 2005; 2: 557-567.
140. Otoguro K, et al. Arisugacins, selective acetylcholinesterase inhibitors of microbial origin. Pharmacol Ther 1997; 76: 45-54.