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Studies on hydrazide–hydrazones derivatives as acetylcholinesterase inhibitors

Year 2015, Volume: 5 Issue: 1, 10 - 14, 03.05.2015

Abstract

Objective: Fifteen hidrazide-hydrazone derivatives were synthesized and evaluated for their ability to inhibit acetylcholinesterase (AChE) using a modification of Ellman’s spectrophotometric method. 

Methods: Anti-acetylcholinesterase activity was evaluated by using a modification of Ellman’sspectrophotometric method. The spectrophotometric method is based on the reaction of released thiocholine to give a coloured product with a chromogenic reagent 5,5-dithio-bis-(2-nitrobenzoic acid).

Results: Among the tested compounds, 4-fluorobenzoic acid [(4-methoxyphenyl) methylene] hydrazide (6) and 2-[(fluorobenzoyl) hydrazono]-1,3-dihydro-indol-3-one (15), showed noteworthy anti-AChE activity when compared to standard drug donepezil (IC50=0.054±0.002µM). 

Conclusion: The anti-AChE activity screening indicated that among the tested compounds, 6 with p-methoxyphenyl substitution and 15 with1,3-dihydro-indol-3-one substitution represent the most active compounds. Based on the activity results, it appears that bulky groups on the hydrazide-hydrazone moiety have made good contribution to the anti-AChE activity.

References

  • Mc Gleenon BM, Dynan KB, Passmore AP. Acetylcholinesterase inhibitors in Alzheimer’sdisease. Br J ClinPharmacol, 1999; 48: 471- 480.
  • Xing, Fu Y, Shi Z, Lu D, Zhang H, Hu Y. Discovery of novel 2,6-disubstituted pyridazinone derivatives as acetylcholinesterase inhibitors. Eur J Med Chem, 2013; 63: 95-103.
  • Alzheimer A. Über eine eigenartige Erkrankung der Hirnrinde (Concerning a noveldisease of the cortex). Allg. Z. Psychiatr. Psychisch-gerichtl. Med. 1907; 64: 146-148.
  • Perry EK, Tomilinson BE, Blessed G, Bergmann K, Gibson PH, Perry RH. Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Br Med J. 1978; 6150: 1457- 1459.
  • Copeland RA. Evaluation of Enzyme Inhibitors in Drug Discovery: A Guide for Medicinal Chemists and Pharmacologists, (Ed. R. Allen Copeland) Wiley-Interscience, Chapter 1, New Jersey, USA, 2005.
  • Copeland RA, Gontarek RR, Luo L. Enzyme Inhibitors: Biostructure- Based and Mechanism-Based Designs in: (Eds.: P. Krogsgaard-Larsen, K. Strİmgaard, U. Madsen) Textbook of Drug Design and Discovery, Chapter 11, CRC Press, Boca Raton, USA, 2010.
  • Shen X. Brain cholinesterases: III. Future perspectives of AD research and clinical practice. Med Hypotheses. 2004; 63: 298-307.
  • Wilkinson DG, Francis PT, Schwam E, Payne-Parrish J. Cholinesterase inhibitors used in the treatment of Alzheimer’s disease: the relationship between pharmacological effects and clinical efficacy. Drugs Aging. 2004; 21: 453-478.
  • Grutzendler J, Morris JC. Cholinesterase inhibitors for Alzheimer’s disease. Drugs. 2001; 61: 41-52.
  • Giacobini E. Cholinesterase: newroles in brain function and Alzheimer’s disease. Neurochem Res. 2003; 28: 515-522.
  • Johannsen P. Long –term cholinesterase inhibitör treatment of Alzheimer’s disease. CNS Drugs. 2004; 18: 757-768.
  • Martinez A, Castro A. Novelcholinesterase inhibitors as future effective drugs for the treatment of Alzheimer’s disease. Expert Opin Investig Drugs. 2006; 15: 1-12.
  • Pepeu G, Giovannini MG. Cholinesterase inhibitors and beyond. Curr Alzheimer Res. 2009; 6: 86-96.
  • Utku S, Gokce M, Orhan I, Sahin MF. Synthesis of novel 6-substituted 3(2H)-pyridazinone-2-acetyl-2-(substituted/-nonsubstitutedbenzal) hydrazone derivatives and acetylcholinesterase and butyryl cholinesterase inhibitory activities in vitro. Arzneimittel-Forsch. 2011; 61: 1-7.
  • Alptuzun V, Prinz M, Horr V, Scheiber J, Radacki K, Fallarero A, Vuorela P, Engels B, Braunschweig H, Erciyas E, Holzgrabe U. Interaction of (benzylidene-hydrazono)-1,4-dihydropyridines with beta-amyloid, acetylcholine, and butyrylcholinesterases. Bioorg Med Chem. 2010; 18: 2049-2059.
  • Gwaram NS, Ali HM, Abdulla MA, Buckle MJC, Sukumaran SD, Chung LY, Othman R, Alhadi AA, Yehye WA, Hadi AHA, Hassandarvish P, Khaledi H, Abdelwahab SI. Synthesis, characterization, X-ray crystallography, acetylcholinesterase inhibition and antioxidant activities of some novel ketone derivatives of gallic hydrazide derived schiffbases. Molecules. 2012; 17: 2408-2427.
  • Ozcelik AB, Gokce M, Orhan I, Kaynak F, Sahin MF. Synthesis and antimicrobial, acetylcholinesterase and butyrylcholinesterase inhibitory activities of novel ester and hydrazide derivatives of 3(2H)-pyridazinone. Arzneimittel-Forsch. 2010; 60: 452-458.
  • Bunyapaiboonsri T, Ramstrom O, Lohmann S, Lehn SM, Peng L, Goeldner M. Dynamic deconvolution of a pre-equilibrated dynamic combinatorial library of acetylcholinesterase inhibitors. Chem Bio Chem. 2001; 2: 438-444.
  • Gholivand K, Hosseini Z, Farshadian S, Naderi-Manesh H. Synthesis, characterization, oxidative degradation, antibacterial activity and acetylcholinesterase/butyrylcholinesterase inhibitory effects of somenewphosphorus (V) hydrazides. Eur J Med Chem. 2010; 45: 5130-5139.
  • Elsinghorst PW, Tanarro CMG, Gutschow M. Novel heterobivalent tacrine derivatives as cholinesterase inhibitors with no table selectivity toward butyrylcholinesterase. J Med Chem. 2006; 49: 7540-7544.
  • Szymański P, Zurek E, Mikiciuk-Olasik E. New tacrine hydrazino nicotinamide hybrids as acetylcholinesterase inhibitors of potential interest for the early diagnostics of Alzheimer’s disease. Pharmazie. 2006; 61: 269-273.
  • Koçyiğit-Kaymakçıoğlu B, Oruç E, Unsalan S, Kandemirli F, Shvets N, Rollas S, Dimoglo A. Synthesis and characterization of novel hydrazide–hydrazones and the study of their structure– antituberculosis activity. Eur J Med Chem. 2006; 41: 1253-1261.
  • Koçyiğit-Kaymakçıoğlu B, Oruç EE, Unsalan S, Rollas S. Antituberculosis activity of hydrazones derivedfrom 4-fluorobenzoic acidhydrazide. Med Chem Res. 2009; 18: 277-286.
  • Ellman GL, Courtney KD, Andres V, Feather-Stone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol. 1961; 7: 88-95.
  • Perry NSL, Houghton PJ, Theobald AE, Jenner P, Perry EK. In-vitroinhibition of human erythrocyte acetyl choline esterase by Salvialav and ula efolia essential oil and constituent terpenes. J Pharm Pharmacol. 2000; 52: 895-902.
  • Freitas L, Silva C, Ellena J, Costa L, Rey NA. Structural and vibrational study of 8-hydroxyquinoline-2-carboxaldehyde isonicotinoylhydrazone-A potential metal-protein attenuating compound (MPAC) for the treatment of Alzheimer’s disease. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 2013; 116: 41-48.
  • Prinz M, Parlar S, Bayraktar G, Alptüzün V, Erciyas E, Fallarero A, Karlsson D, Vuorela P, Burek M, Förster C, Turunc E, Armagan G, Yalcin A, Schiller C, Leuner K, Krug M, Sotriffer CA, Holzgrabe U. 1,4-Substituted 4-(1H)-pyridylene-hydrazone-typeinhibitors of AChE, BuChE, andamyloid-b aggregation crossing the blood–brain barrier. Eur J Pharm Sci. 2013; 49: 603-613.

Asetilkolin esteraz inhibitörü olan hidrazid hidrazonlar üzerinde çalışmalar

Year 2015, Volume: 5 Issue: 1, 10 - 14, 03.05.2015

Abstract

Amaç: On beş adet hidrazit-hidrazon türevi sentezlenmiş ve asetilkolinesteraz enzimini (AChE) inhibe etme yetenekleri Ellman’ın modifiye spektrofotometrik yöntemi ile değerlendirilmiştir. 

Yöntem: Anti-asetilkolinesteraz aktivite tayini Ellman’ın modifiye edilmiş spektrofotometrik yöntemi kullanılarak yapılmıştır. Bu spektrofotometrik yöntem bir kromojenik reaktif olan 5,5-ditiyo-bis-(2-nitrobenzoik asit) ile salınan tiyokolinin renkli bir ürün vermesi esasına dayanır. 

Bulgular: Test edilen bileşikler arasında, 4-fluorobenzoik asit [(4-metoksifenil) metilen] hidrazid(6) ve 2-[(fluorobenzoil) hidrazono]-1,3-dihidro-indol-3-on (15), referans ilaç donezepil (IC50=0.054±0.002µM) ile kıyaslandığında kayda değer anti-AChE aktivite göstermiştir. 

Sonuç: Anti- AChE aktivite sonuçları, p-metoksifenil sübstitüenti taşıyan bileşik 6 ve 1,3-dihidro-indol-3-on sübstitüenti taşıyan bileşik 15’in en aktif bileşikler olduğunu göstermiştir. Aktivite sonuçlarından, hidrazid-hidrazon yapısı üzerinde hacimli grupların bulunmasının anti- AChE aktiviteye olumlu yönde katkıda bulunduğu görülmektedir.

References

  • Mc Gleenon BM, Dynan KB, Passmore AP. Acetylcholinesterase inhibitors in Alzheimer’sdisease. Br J ClinPharmacol, 1999; 48: 471- 480.
  • Xing, Fu Y, Shi Z, Lu D, Zhang H, Hu Y. Discovery of novel 2,6-disubstituted pyridazinone derivatives as acetylcholinesterase inhibitors. Eur J Med Chem, 2013; 63: 95-103.
  • Alzheimer A. Über eine eigenartige Erkrankung der Hirnrinde (Concerning a noveldisease of the cortex). Allg. Z. Psychiatr. Psychisch-gerichtl. Med. 1907; 64: 146-148.
  • Perry EK, Tomilinson BE, Blessed G, Bergmann K, Gibson PH, Perry RH. Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Br Med J. 1978; 6150: 1457- 1459.
  • Copeland RA. Evaluation of Enzyme Inhibitors in Drug Discovery: A Guide for Medicinal Chemists and Pharmacologists, (Ed. R. Allen Copeland) Wiley-Interscience, Chapter 1, New Jersey, USA, 2005.
  • Copeland RA, Gontarek RR, Luo L. Enzyme Inhibitors: Biostructure- Based and Mechanism-Based Designs in: (Eds.: P. Krogsgaard-Larsen, K. Strİmgaard, U. Madsen) Textbook of Drug Design and Discovery, Chapter 11, CRC Press, Boca Raton, USA, 2010.
  • Shen X. Brain cholinesterases: III. Future perspectives of AD research and clinical practice. Med Hypotheses. 2004; 63: 298-307.
  • Wilkinson DG, Francis PT, Schwam E, Payne-Parrish J. Cholinesterase inhibitors used in the treatment of Alzheimer’s disease: the relationship between pharmacological effects and clinical efficacy. Drugs Aging. 2004; 21: 453-478.
  • Grutzendler J, Morris JC. Cholinesterase inhibitors for Alzheimer’s disease. Drugs. 2001; 61: 41-52.
  • Giacobini E. Cholinesterase: newroles in brain function and Alzheimer’s disease. Neurochem Res. 2003; 28: 515-522.
  • Johannsen P. Long –term cholinesterase inhibitör treatment of Alzheimer’s disease. CNS Drugs. 2004; 18: 757-768.
  • Martinez A, Castro A. Novelcholinesterase inhibitors as future effective drugs for the treatment of Alzheimer’s disease. Expert Opin Investig Drugs. 2006; 15: 1-12.
  • Pepeu G, Giovannini MG. Cholinesterase inhibitors and beyond. Curr Alzheimer Res. 2009; 6: 86-96.
  • Utku S, Gokce M, Orhan I, Sahin MF. Synthesis of novel 6-substituted 3(2H)-pyridazinone-2-acetyl-2-(substituted/-nonsubstitutedbenzal) hydrazone derivatives and acetylcholinesterase and butyryl cholinesterase inhibitory activities in vitro. Arzneimittel-Forsch. 2011; 61: 1-7.
  • Alptuzun V, Prinz M, Horr V, Scheiber J, Radacki K, Fallarero A, Vuorela P, Engels B, Braunschweig H, Erciyas E, Holzgrabe U. Interaction of (benzylidene-hydrazono)-1,4-dihydropyridines with beta-amyloid, acetylcholine, and butyrylcholinesterases. Bioorg Med Chem. 2010; 18: 2049-2059.
  • Gwaram NS, Ali HM, Abdulla MA, Buckle MJC, Sukumaran SD, Chung LY, Othman R, Alhadi AA, Yehye WA, Hadi AHA, Hassandarvish P, Khaledi H, Abdelwahab SI. Synthesis, characterization, X-ray crystallography, acetylcholinesterase inhibition and antioxidant activities of some novel ketone derivatives of gallic hydrazide derived schiffbases. Molecules. 2012; 17: 2408-2427.
  • Ozcelik AB, Gokce M, Orhan I, Kaynak F, Sahin MF. Synthesis and antimicrobial, acetylcholinesterase and butyrylcholinesterase inhibitory activities of novel ester and hydrazide derivatives of 3(2H)-pyridazinone. Arzneimittel-Forsch. 2010; 60: 452-458.
  • Bunyapaiboonsri T, Ramstrom O, Lohmann S, Lehn SM, Peng L, Goeldner M. Dynamic deconvolution of a pre-equilibrated dynamic combinatorial library of acetylcholinesterase inhibitors. Chem Bio Chem. 2001; 2: 438-444.
  • Gholivand K, Hosseini Z, Farshadian S, Naderi-Manesh H. Synthesis, characterization, oxidative degradation, antibacterial activity and acetylcholinesterase/butyrylcholinesterase inhibitory effects of somenewphosphorus (V) hydrazides. Eur J Med Chem. 2010; 45: 5130-5139.
  • Elsinghorst PW, Tanarro CMG, Gutschow M. Novel heterobivalent tacrine derivatives as cholinesterase inhibitors with no table selectivity toward butyrylcholinesterase. J Med Chem. 2006; 49: 7540-7544.
  • Szymański P, Zurek E, Mikiciuk-Olasik E. New tacrine hydrazino nicotinamide hybrids as acetylcholinesterase inhibitors of potential interest for the early diagnostics of Alzheimer’s disease. Pharmazie. 2006; 61: 269-273.
  • Koçyiğit-Kaymakçıoğlu B, Oruç E, Unsalan S, Kandemirli F, Shvets N, Rollas S, Dimoglo A. Synthesis and characterization of novel hydrazide–hydrazones and the study of their structure– antituberculosis activity. Eur J Med Chem. 2006; 41: 1253-1261.
  • Koçyiğit-Kaymakçıoğlu B, Oruç EE, Unsalan S, Rollas S. Antituberculosis activity of hydrazones derivedfrom 4-fluorobenzoic acidhydrazide. Med Chem Res. 2009; 18: 277-286.
  • Ellman GL, Courtney KD, Andres V, Feather-Stone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol. 1961; 7: 88-95.
  • Perry NSL, Houghton PJ, Theobald AE, Jenner P, Perry EK. In-vitroinhibition of human erythrocyte acetyl choline esterase by Salvialav and ula efolia essential oil and constituent terpenes. J Pharm Pharmacol. 2000; 52: 895-902.
  • Freitas L, Silva C, Ellena J, Costa L, Rey NA. Structural and vibrational study of 8-hydroxyquinoline-2-carboxaldehyde isonicotinoylhydrazone-A potential metal-protein attenuating compound (MPAC) for the treatment of Alzheimer’s disease. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 2013; 116: 41-48.
  • Prinz M, Parlar S, Bayraktar G, Alptüzün V, Erciyas E, Fallarero A, Karlsson D, Vuorela P, Burek M, Förster C, Turunc E, Armagan G, Yalcin A, Schiller C, Leuner K, Krug M, Sotriffer CA, Holzgrabe U. 1,4-Substituted 4-(1H)-pyridylene-hydrazone-typeinhibitors of AChE, BuChE, andamyloid-b aggregation crossing the blood–brain barrier. Eur J Pharm Sci. 2013; 49: 603-613.
There are 27 citations in total.

Details

Primary Language Turkish
Journal Section Articles
Authors

Usame Abu Mohsen This is me

Bedia Koçyiğit Kaymakçıoğlu

Emine Elçin Oruç Emre This is me

Zafer Asım Kaplancıklı This is me

Sevim Rollas This is me

Publication Date May 3, 2015
Submission Date May 3, 2015
Published in Issue Year 2015 Volume: 5 Issue: 1

Cite

APA Abu Mohsen, U., Koçyiğit Kaymakçıoğlu, B., Oruç Emre, E. E., Kaplancıklı, Z. A., et al. (2015). Asetilkolin esteraz inhibitörü olan hidrazid hidrazonlar üzerinde çalışmalar. Clinical and Experimental Health Sciences, 5(1), 10-14. https://doi.org/10.5455/musbed.20141117035707
AMA Abu Mohsen U, Koçyiğit Kaymakçıoğlu B, Oruç Emre EE, Kaplancıklı ZA, Rollas S. Asetilkolin esteraz inhibitörü olan hidrazid hidrazonlar üzerinde çalışmalar. Clinical and Experimental Health Sciences. October 2015;5(1):10-14. doi:10.5455/musbed.20141117035707
Chicago Abu Mohsen, Usame, Bedia Koçyiğit Kaymakçıoğlu, Emine Elçin Oruç Emre, Zafer Asım Kaplancıklı, and Sevim Rollas. “Asetilkolin Esteraz inhibitörü Olan Hidrazid Hidrazonlar üzerinde çalışmalar”. Clinical and Experimental Health Sciences 5, no. 1 (October 2015): 10-14. https://doi.org/10.5455/musbed.20141117035707.
EndNote Abu Mohsen U, Koçyiğit Kaymakçıoğlu B, Oruç Emre EE, Kaplancıklı ZA, Rollas S (October 1, 2015) Asetilkolin esteraz inhibitörü olan hidrazid hidrazonlar üzerinde çalışmalar. Clinical and Experimental Health Sciences 5 1 10–14.
IEEE U. Abu Mohsen, B. Koçyiğit Kaymakçıoğlu, E. E. Oruç Emre, Z. A. Kaplancıklı, and S. Rollas, “Asetilkolin esteraz inhibitörü olan hidrazid hidrazonlar üzerinde çalışmalar”, Clinical and Experimental Health Sciences, vol. 5, no. 1, pp. 10–14, 2015, doi: 10.5455/musbed.20141117035707.
ISNAD Abu Mohsen, Usame et al. “Asetilkolin Esteraz inhibitörü Olan Hidrazid Hidrazonlar üzerinde çalışmalar”. Clinical and Experimental Health Sciences 5/1 (October 2015), 10-14. https://doi.org/10.5455/musbed.20141117035707.
JAMA Abu Mohsen U, Koçyiğit Kaymakçıoğlu B, Oruç Emre EE, Kaplancıklı ZA, Rollas S. Asetilkolin esteraz inhibitörü olan hidrazid hidrazonlar üzerinde çalışmalar. Clinical and Experimental Health Sciences. 2015;5:10–14.
MLA Abu Mohsen, Usame et al. “Asetilkolin Esteraz inhibitörü Olan Hidrazid Hidrazonlar üzerinde çalışmalar”. Clinical and Experimental Health Sciences, vol. 5, no. 1, 2015, pp. 10-14, doi:10.5455/musbed.20141117035707.
Vancouver Abu Mohsen U, Koçyiğit Kaymakçıoğlu B, Oruç Emre EE, Kaplancıklı ZA, Rollas S. Asetilkolin esteraz inhibitörü olan hidrazid hidrazonlar üzerinde çalışmalar. Clinical and Experimental Health Sciences. 2015;5(1):10-4.

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