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Synthesis and biological evaluation of some tacrine analogs: study of the effect of the chloro substituent on the acetylcholinesterase inhibitory activity

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Abstract

New tetrahydroquinoline derivatives were synthesized, characterized, and evaluated for their in vitro and in vivo acetylcholinesterase inhibitory activity as well as hepatotoxicity using tacrine as a reference standard. The obtained results revealed that most of the compounds comprising a chloro substituent displayed higher activity when compared with the other analogs. Among the newly synthesized compounds, four analogs displayed in vitro and in vivo acetylcholinesterase inhibitory activity comparable to or slightly higher than tacrine. Among these compounds, the 2-chlorotetrahydroquinoline derivative emerged with hepatotoxicity results comparable to saline.

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References

  1. Samadi A, Marco-Contelles J, Soriano E, Alvarez-Perez M, Chioua M, Romero A, Gonzalez-Lafuente L, Gandia L, Roda JM, Lopez MG, Villarroya M, Garcia AG, De Los Rios C (2010) Bioorg Med Chem 18:5861

  2. Wecker L, Crespo L, Dunaway G, Faingold C, Watts S (2010) Brody’s Human Pharmacology, 5th edn. Mosby, Philadelphia

    Google Scholar 

  3. Romero A, Cacabelos R, Oset-Gasque MJ, Samadi A, Marco-Contelles J (2013) Bioorg Med Chem Lett 23:1916

  4. Burns A, Iliffe S (2009) Br Med J 338:b158

    Article  Google Scholar 

  5. Goedert M, Spillantini MG (2006) Science 314:777

    Article  CAS  Google Scholar 

  6. Tumiatti V, Minarini A, Bolognesi ML, Milelli A, Rosini M, Melchiorre C (2010) Curr Med Chem 17:1825

    Article  CAS  Google Scholar 

  7. Castro A, Martinez A (2006) Curr Pharm Des 12:4377

    Article  CAS  Google Scholar 

  8. Rang HP, Ritter JM, Flower RJ, Henderson G (2015) Rang & Dale’s pharmacology, 8th edn. Churchill Livingstone, London

  9. Felder CC, Bymaster FP, Ward J, Delapp N (2000) J Med Chem 43:4333

  10. Terry AV Jr, Buccafusco JJ (2003) J Pharmacol Exp Ther 306:821

    Article  CAS  Google Scholar 

  11. Gualtieri F, Dei S, Manetti D, Romanelli MN, Scapecchi S, Teodori E (1995) Farmaco 50:489

    CAS  Google Scholar 

  12. Hardy J (2009) J Neurochem 110:1129

    Article  CAS  Google Scholar 

  13. Gong CX, Iqbal K (2008) Curr Med Chem 15:2321

    Article  CAS  Google Scholar 

  14. Webber KM, Raina AK, Marlatt MW, Zhu X, Prat MI, Morelli L, Casadesus G, Perry G, Smith MA (2005) Mech Ageing Dev 126:1019

    Article  CAS  Google Scholar 

  15. Muñoz-Torrero D, Camps P (2006) Curr Med Chem 13:399

    Article  Google Scholar 

  16. Zemek F, Drtinova L, Nepovimova E, Sepsova V, Korabecny J, Klimes J, Kuca K (2014) Expert Opin Drug Saf 13:759

    CAS  Google Scholar 

  17. Rizzo S, Riviere C, Piazzi L, Bisi A, Gobbi S, Bartolini M, Andrisano V, Morroni F, Tarozzi A, Monti JP, Rampa A (2008) J Med Chem 51:2883

    Article  CAS  Google Scholar 

  18. Wang X-D, Chen X-Q, Yang H-H, Hu GY (1999) Neurosci Lett 272:21

    Article  CAS  Google Scholar 

  19. Hier DB (1997) Surg Neurol 47:84

    CAS  Google Scholar 

  20. Munson PL, Mueller RA, Breese GR (1996) Principles of pharmacology: basic concepts and clinical applications. Chapman and Hall, London

    Google Scholar 

  21. Camps P, El Achab R, Gorbig DM, Morral J, Munoz-Torrero D, Badia A, Banos JE, Vivas NM, Barril X, Orozco M, Luque FJ (1999) J Med Chem 42:3227

    Article  CAS  Google Scholar 

  22. Kaul PN (1962) J Pharm Pharmacol 14:243

    Article  CAS  Google Scholar 

  23. McKenna MT, Proctor GR, Young LC, Harvey AL (1997) J Med Chem 40:3516

    Article  CAS  Google Scholar 

  24. Soukup O, Jun D, Zdarova-Karasova J, Patocka J, Musilek K, Korabecny K, Krusek J, Kaniakova M, Sepsova V, Mandikova J, Trejtnar F, Pohanka M, Drtinova L, Pavlik M, Tobin G, Kuca K (2013) Curr Alzheimer Res 10:893

    Article  CAS  Google Scholar 

  25. Koda-Kimble MA, Alldredge BK (2013) Applied therapeutics: the clinical use of drugs, 10th edn. Wolters Kluwer/Lippincott Williams and Wilkins, Philadelphia

    Google Scholar 

  26. Pang Y, Quiram P, Jelacic T, Hong F, Brimijoin S (1996) J Biol Chem 271:23646

    Article  CAS  Google Scholar 

  27. El-Tombary AA, Omar A, Eshba NH, Rostom S, Ragab HM, Saad E (2008) Alex J Pharm Sci 22:61

    CAS  Google Scholar 

  28. Gregor VE, Emmerling MR, Lee C, Moore CJ (1992) Bioorg Med Chem Lett 2:861

    Article  CAS  Google Scholar 

  29. Erdelyi M (2012) Chem Soc Rev 41:3547

    Article  CAS  Google Scholar 

  30. Saito K, Kambe S, Sakurai A, Midorikawa H (1981) Synthesis 1981:211

    Article  Google Scholar 

  31. Ghorab MM, Heiba HI, Amin NE (1999) Pharmazie 54:226

    CAS  Google Scholar 

  32. Moustafa AH, Said SA, Haikal AZ (2014) Nucleosides. Nucleotides Nucleic Acids 33:111

    Article  CAS  Google Scholar 

  33. Kambe S, Saito K, Sakurai A, Midorikawa H (1980) Synthesis 1980:366

    Article  Google Scholar 

  34. Wan Y (2011) Synth Commun 41:2997

    Article  CAS  Google Scholar 

  35. Abd El-Salam OI (2009) Pharmazie 64:147

  36. Azzam SHS, Siddekha A, Pasha MA (2012) Tetrahedron Lett 53:6306

    Article  CAS  Google Scholar 

  37. Perry WLM (1970) Pharmacological experiments on isolated preparations, 2nd edn. Churchill Livingstone, London

    Google Scholar 

  38. Rall TW, Nies AS Taylor P (2011) Goodman and Gillman’s the pharmacological basis of therapeutics, 12th edn. McGraw-Hill Medical, New York

  39. Ellman G, Courtney D, Andres V, Featherstone RM (1961) Biochem Pharmacol 7:88

    Article  CAS  Google Scholar 

  40. Burtis CA, Ashwood ER, Bruns DE (2008) Tietz fundamentals of clinical chemistry, 6th edn. WB Saunders, Philadelphia

    Google Scholar 

  41. Kumar KS, Kumar KLS (2010) Der Pharmacia Lettre 2:261

    Google Scholar 

  42. Raju NJ, Sreekanth N (2011) Int J Res Ayurveda Pharm 2:166

    Google Scholar 

  43. Hamulakova S, Janovec L, Hrabinova M, Kristian P, Kuca K, Banasova M, Imrich J (2012) Eur J Med Chem 55:23

    Article  CAS  Google Scholar 

  44. Chemical Computing Group Inc (2009) Molecular operating environment (MOE) 2009.10. Montreal, Canada. http://www.chemcomp.com. Accessed 23 Sept 2015

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt

    Hanan M. Ragab & Hayam M. A. Ashour

  2. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt

    Amal Galal

  3. Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Beirut Arab University, Beirut, Lebanon

    Amal Galal, Asser I. Ghoneim & Hassan R. Haidar

  4. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt

    Asser I. Ghoneim

Authors
  1. Hanan M. Ragab
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  2. Hayam M. A. Ashour
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  3. Amal Galal
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  4. Asser I. Ghoneim
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  5. Hassan R. Haidar
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Correspondence to Hanan M. Ragab.

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Ragab, H.M., Ashour, H.M.A., Galal, A. et al. Synthesis and biological evaluation of some tacrine analogs: study of the effect of the chloro substituent on the acetylcholinesterase inhibitory activity. Monatsh Chem 147, 539–552 (2016). https://doi.org/10.1007/s00706-015-1641-2

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  • DOI: https://doi.org/10.1007/s00706-015-1641-2

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