In vitro inhibitory profile of NDGA against AChE and its in silico structural modifications based on ADME profile

详细信息    查看全文

• 作者：Chandran Remya (1)
  Kalarickal Vijayan Dileep (1)
  Ignatius Tintu (1)
  Elessery Jayadevi Variyar (1)
  Chittalakkottu Sadasivan (1)
  
• 关键词：Acetylcholinesterase ; NDGA ; ADME ; CNS activity ; Induced fit docking
• 刊名：Journal of Molecular Modeling
• 出版年：2013
• 出版时间：March 2013
• 年：2013
• 卷：19
• 期：3
• 页码：1179-1194
• 全文大小：967KB
• 参考文献：1. Selkoe DJ, Schenk D (2003) Alzheimer’s disease: molecular understanding predicts amyloid-based therapeutics. Annu Rev Pharmacol Toxicol 43:545-84 CrossRef
  2. Schliebs R (2005) Basal forebrain cholinergic dysfunction in Alzheimer’s disease–interrelationship with beta-amyloid, inflammation and neurotrophin signaling. Neurochem Res 30:895-08 CrossRef
  3. Goedert M, Spillantini MG (2006) A century of Alzheimer’s disease. Science 314:777-81 CrossRef
  4. Luttmann E, Linnemann E, Fels G (2002) Galantamine as bis-functional ligand for the acetylcholinesterase. J Mol Model 8:208-16 CrossRef
  5. Schrattenholz A, Pereira EF, Roth U, Weber KH, Albuquerque EX, Maelicke A (1996) Agonist responses of neuronal nicotinic acetylcholine receptors are potentiated by a novel class of allosterically acting ligands. Mol Pharmacol 49:1-
  6. Coyle JT, Geerts H, Sorra K, Amatniek J (2007) Beyond in vitro data: a review of in vivo evidence regarding the allosteric potentiating effect of galantamine on nicotinic acetylcholine receptors in Alzheimer’s neuropathology. J Alzheimers Dis 11:491-07
  7. Reyes AE, Chacon MA, Dinamarca MC, Cerpa W, Morgan C, Inestrosa NC (2004) Acetylcholinesterase—Abeta complexes are more toxic than Abeta fibrils in rat hippocampus: effect on rat beta-amyloid aggregation, laminin expression, reactive astrocytosis, and neuronal cell loss. Am J Pathol 164:2163-174 CrossRef
  8. Castro A, Martinez A (2006) Targeting beta-amyloid pathogenesis through acetylcholinesterase inhibitors. Curr Pharm Des 12:4377-387 CrossRef
  9. Kasa P, Papp H, Kasa P Jr, Torok I (2000) Donepezil dose-dependently inhibits acetylcholinesterase activity in various areas and in the presynaptic cholinergic and the postsynaptic cholinoceptive enzyme-positive structures in the human and rat brain. Neuroscience 101:89-00 CrossRef
  10. Kurz A (1998) The therapeutic potential of tacrine. J Neural Transm Suppl 54:295-99
  11. Sugimoto H (2001) Donepezil hydrochloride: a treatment drug for Alzheimer’s disease. Chem Rec 1(1):63-3 CrossRef
  12. Zarotsky V, Sramek JJ, Cutler NR (2003) Galantamine hydrobromide: an agent for alzheimer’s disease. Am J Health Syst Pharm 60:446-52
  13. Jann MW (2000) Rivastigmine, a new- generation cholinesterase inhibitor for the treatment of Alzheimer’s disease. Pharmacotherapy 20(1):1-2 CrossRef
  14. Francis PT, Nordberg A, Arnold SE (2005) A preclinical view of cholinesterase inhibitors in neuroprotection: do they provide more than symptomatic benefits in Alzheimer’s disease? Trends Pharmacol Sci 26:104-11 CrossRef
  15. Wang YE, Yue DX, Tang XC (1986) Anticholinesterase activity of huperzine A. Acta pharmacol Sin 7:110-13
  16. Barak D, Ordentlich A, Stein D, Yu QS, Greig NH, Shafferman A (2009) Accommodation of physostigmine and its analogs by acetylcholinesterase is dominated by hydrophobic interactions. Biochem J 417(1):213-22 CrossRef
  17. Arteaga S, Andrade-Cetto A, Cardenas R (2005) / Larrea tridentate (creosote bush) an abundant palnt of Mexican and US-american desert and its metabolite nordihydroguairetic acid. J Ethnopharmol 98(3):231-39 CrossRef
  18. Oliveto EP (1972) Nordihydroguaiaretic acid. A naturally occurring antioxidant. Chem Ind 17:677-79
  19. Noor R, Mittal S, Iqbal J (2002) Superoxide dismutase-applications and relevance to human diseases. Med Sci Monit 8:RA210–RA215
  20. Guzman-Beltran S, Espada S, Orozco-Ibarra M, Pedraza-Chaverri J, Cuadrado A (2008) Nordihydroguaiaretic acid activates the antioxidant pathway Nrf2/HO-1 and protects cerebellargranule neurons against oxidative stress. Neurosci Lett 447:167-71 CrossRef
  21. Goodman Y, Steiner MR, Steiner SM, Mattson MP (1994) Nordihydroguaiaretic acid protects hippocampal neurons against amyloid beta-peptide toxicity, and attenuates free radical and calcium accumulation. Brain Res 654:171-76 CrossRef
  22. Rothman SM, Yamada KA, Lancaster N (1993) Nordihydroguaiaretic acid attenuates NMDA neurotoxicity—action beyond the receptor. Neuropharmacology 32:1279-288 CrossRef
  23. Boston-Howes W, Williams EO, Bogush A, Scolere M, Pasinelli P, Trotti D (2008) Nordihydroguaiaretic acid increases glutamate uptake in vitro and in vivo: therapeutic implications for amyotrophic lateral sclerosis. Exp Neurol 213:229-37 CrossRef
  24. Shishido Y, Furushiro M, Hashimoto S, Yokokura T (2001) Effect of nordihydroguaiaretic acid on behavioral impairment and neuronal cell death after forebrain ischemia. Pharmacol Biochem Behav 69:469-74 CrossRef
  25. Majumdar DK, Govil JN, Singh VK (2003) Recent progress in medicinal plants. Vol 8 Phytochemistry and Pharmacology. Studium, Houston, TX
  26. Ellman GL, Courtney KD, Andres V Jr, Featherstone RM (1961) Biochem Pharmacol 7:88-5 CrossRef
  27. Sussman JL, Harel M, Frolow F, Oefner C, Goldman A, Toker L, Silman I (1991) Science 253:872-79 CrossRef
  28. Bon S, Vigny M, Massoulie J (1979) Asymmetric and globular forms of acetylcholinesterase in mammals and birds. Proc Natl Acad Sci USA 76:2546-550 CrossRef
  29. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (2001) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 46:3-6 CrossRef
  30. Ekins S, Waller CL, Swann PW, Cruciani G, Wrighton SA, Wikel JH (2000) J Pharmacol Toxicol 44:251-72 CrossRef
  31. Alavijeh MS, Chishty M, Qaiser MZ, Palmer AM (2005) Drug metabolism and pharmacokinetics, the blood-brain barrier, and central nervous system drug discovery. NeuroRx 2:554-71
  32. Clark DE (2003) In silico prediction of blood–brain barrier permeation. Drug Discov Today 8:927-33 CrossRef
  33. Lloyd EJ, Andrews PR (1986) A common structural model for central nervous system drugs and their receptors. J Med Chem 29:453-62 CrossRef
  34. Lemke TL, Williams DA, Roche VF, Zito SW (2008), Foye’s principles of medicinal chemistry. Wolters Kluwer/Lippincott Williams and Wilkins, Baltimore
  35. Pajouhesh H, Lenz GR (2005) Medicinal chemical properties of successful central nervous system drugs. NeuroRx 2:541-53 CrossRef
  36. Clark DE (1999) Rapid calculation of polar molecular surface area and its application to the prediction of transport phenomena. 2. Prediction of blood–brain barrier penetration. J Pharm Sci 88:815-21 CrossRef
  37. Ajay, Bemis GW, Murcko MA (1999) Designing libraries with CNS activity. J Med Chem 42:4942-951 CrossRef
  38. Balon K, Riebesehl BU, Muller BW (1999) Determination of liposome partitioning of ionizable drugs by titration. J Pharm Sci 88:802-06 CrossRef
  39. Bhal SK, Kassam K, Peirson IG, Pearl GM (2007) The rule of five revisited: applying log d in place of log p in drug-likeness filters. Mol Pharmaceut 4:556-60 CrossRef
  40. Garberg P, Ball M, Borg N, Cecchelli R, Fenart L, Hurst RD, Lindmark T, Mabondzo A, Nilsson JE, Raub TJ, Stanimirovic D, Terasaki T, Oberg JO (2005) In vitro models for the blood–brain barrier. Toxicol In Vitro 19:299-34 CrossRef
  41. Deli MA, Abraham CS, Kataoka Y, Niwa M (2005) Permeability studies on in vitro blood–brain barrier models: physiology, pathology, and pharmacology. Cell Mol Neurobiol 25:59-27 CrossRef
  42. Reichel A, Begley DJ, Abbott NJ (2003) An overview of in vitro techniques for blood–brain barrier studies. Methods Mol Med 89:307-24
  43. Doan KM, Humphreys JE, Webster LO, Wring SA, Shampine LJ, Serabjit-Singh CJ (2002) Passive permeability and P-glycoproteinmediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs. J Pharmacol Exp Ther 303:1029-037 CrossRef
  
• 作者单位：Chandran Remya (1)
  Kalarickal Vijayan Dileep (1)
  Ignatius Tintu (1)
  Elessery Jayadevi Variyar (1)
  Chittalakkottu Sadasivan (1)
  
  1. Department of Biotechnology and Microbiology and Inter University Centre for Biosciences, Kannur University, Thalassery Campus, Palayad P.O., Kerala, 670661, India
  
• ISSN：0948-5023

文摘

Acetylcholinesterase (AChE) inhibitors are currently in focus for the pharmacotherapy of Alzheimer’s disease (AD). These inhibitors increase the level of acetylcholine in the brain and facilitate cholinergic neurotransmission. AChE inhibitors such as rivastigmine, galantamine, physostigmine and huperzine are obtained from plants, indicating that plants can serve as a potential source for novel AChE inhibitors. We have performed a virtual screening of diverse natural products with distinct chemical structure against AChE. NDGA was one among the top scored compounds and was selected for enzyme kinetic studies. The IC50 of NDGA on AChE was 46.2?μM. However, NDGA showed very poor central nervous system (CNS) activity and blood–brain barrier (BBB) penetration. In silico structural modification on NDGA was carried out in order to obtain derivatives with better CNS activity as well as BBB penetration. The studies revealed that some of the designed compounds can be used as lead molecules for the development of drugs against AD Figure Inhibitory activity of NDGA against AChE