Abstract
Objective: In this study we aimed to synthesize some hydrazone derivatives of thiazole and to evaluate their anticholinesterase activities.
Method: Pyrrole-2-carboxaldehydes were reacted directly with thiosemicarbazide in ethanol and then obtained thiosemicarbazones were condensed with ?-bromoacetophenone derivatives (Hantzsch reaction) to give 1-substituted pyrrole-2-carboxaldehyde (4-(4-substituted phenyl)-1,3-thiazol-2-yl) hydrazones. The structures of the obtained compounds were elucidated by using IR, 1H-NMR and FAB+-MS spectral data and elemental analyses results. In the pharmacological studies, anticholinesterase activities of these compounds have been evaluated by using modified Ellman’s spectrophotometric method.
Results: The compound (1) can be identified as the most active anticholinesterase molecule due to its inhibitory effect on acetylcholinesterase with inhibition percentages of 64.10 (1 mM) and 33.00 (0.1 mM) % and also IC50 value of 0.59 mM.
Conclusion: The substitutions on phenyl ring at para position and at first position of pyrrole ring have negatively affected anticholinesterase activity.
References
- Aderinwale GO, Ernst HW, Mousa SA. Current therapies and new strategies for the management of Alzheimer’s Disease. Am J Alzheimers Dis Other Demen. 2012;25: 414-424.
- Dipiro J, Talbert RL, Yee GC, Matzke GR, Wells BG. Alzheimer’s disease. In: Jennifer Dea, eds. Pharmacotherapy: A Pathophysiology Approach. New York: NY McGraw-Hill; 2005.
- Salloway S, Correia S. Alzheimer disease: time to improve its diagnosis and treatment. Cleve Clin J Med. 2009;76(1): 49-58.
- Terry Jr. AV, Buccafusco JJ. The cholinergic hypothesis of age and Alzheimer’s disease-related cognitive deficits: recent challenges and their implications for novel drug development. J Pharmacol Exp Ther. 2003;306: 821-827.
- Selkoe DJ. Alzheimer’s disease: genes, proteins, and therapy. Physiol Rev. 2001; 81: 741-766.
- Giacobini E. Cholinesterase inhibitors: new roles and therapeutic alternatives. Pharmacol Res. 2004; 5: 433-440.
- Asadipour A, Alipour M, Jafari M, Khoobi M, Emami S, Nadri H, Sakhteman A, Moradi A, Sheibani V, Moghadam FH, Shafiee A, Foroumadi A. Novel coumarin-3-carboxamides bearing N-benzylpiperidine moiety as potent acetylcholinesterase inhibitors. Eur J Med Chem. 2013; 70: 623-630.
- Siddiqui N, Arshad MF, Ahsan W, Alam MS. Thiazoles: a valuable insight into the recent advances and biological activities. Int J Pharm Sci Drug Res. 2009; 1: 136-143.
- Mustafa SM, Naira VA, Chittoorb JP, Krishnapillaic S. Synthesis of 1,2,4-triazoles and thiazoles from thiosemicarbazide and its derivatives. Mini-Rev Org Chem. 2004;1: 375-385.
- Andreani A, Burnelli S, Granaiola M, Guardigli M, Leoni A, Locatelli A, Morigi R, Rambaldi M, Rizzoli M, Varoli L, Roda A. Chemiluminescent high-throughput microassay applied to imidazo [2,1-b]thiazole derivatives as potential acetylcholinesterase and butyrylcholinesterase inhibitors. Eur J Med Chem. 2008;43: 657-661. Sengupta AK, Garg M. New 5-arylamino-2[N-(2’mercaptoacetylamino-4’-arylthiazolo)]thiadiazoles(III): as AChE inhibitors. J Indian Chem Soc. 1980;57: 1241-1243.
- Shaw FH, Bentley GA. The pharmacology of some new anticholinesterases. Aust J Exp Biol Med Sci. 1953;31: 573–576.
- Matsunaga Y, Tanaka T, Yoshinaga K, Ueki S, Hori Y, Eta R. Acotiamide hydrochloride (Z-338), a new selective acetylcholinesterase inhibitor, enhances gastric motility without prolonging QT interval in dogs: comparison with cisapride, itopride, and mosapride. J Pharmacol Exp Ther. 2011;336: 791-800.
Abstract
Amaç: Bu çalışmada, tiyazolün bazı hidrazon türevlerinin sentezlerinin ve antikolinesteraz aktivitelerinin araştırılması amaçlandı.
Yöntem: Pirol-2-karboksaldehidler tiyosemikarbazit ile etanol içinde direkt olarak reaksiyona tabi tutuldu ve oluşan tiyosemikarbazon, ?-bromoasetofenon türevleri ile (Hantzsch reaction) kondanse edilerek, 1-sübstitüe pirol-2-karboksaldehid (4-(4-sübstitüe fenil)-1,3-tiyazol-2-il)hidrazon türevlerini verdi. Bileşiklerin kimyasal yapıları, IR, 1H-NMR ve FAB+-MS spektral verileri ve elementel analiz verileri ile aydınlatıldı. Modifiye edilmiş Ellman spektrofotometrik metodu kullanılarak, elde edilen tüm bileşiklerin asetilkolinesteraz (AChE) inhibisyonları incelendi.
Bulgular: Bileşik 1, AChE üzerinde %64.10 (1 mM) and 33.00 (0.1 mM) inhibisyon oranları ve IC50=0.59 mM değeri ile en aktif antikolinesteraz molekül olarak belirlenmiştir.
Sonuçlar: Fenil halkası üzerinde para konumundan ve pirol halkasının 1. konumundan sübstitüsyonlar antikolinesteraz etkiyi negatif yönde etkilemiştir.
Keywords
References
- Aderinwale GO, Ernst HW, Mousa SA. Current therapies and new strategies for the management of Alzheimer’s Disease. Am J Alzheimers Dis Other Demen. 2012;25: 414-424.
- Dipiro J, Talbert RL, Yee GC, Matzke GR, Wells BG. Alzheimer’s disease. In: Jennifer Dea, eds. Pharmacotherapy: A Pathophysiology Approach. New York: NY McGraw-Hill; 2005.
- Salloway S, Correia S. Alzheimer disease: time to improve its diagnosis and treatment. Cleve Clin J Med. 2009;76(1): 49-58.
- Terry Jr. AV, Buccafusco JJ. The cholinergic hypothesis of age and Alzheimer’s disease-related cognitive deficits: recent challenges and their implications for novel drug development. J Pharmacol Exp Ther. 2003;306: 821-827.
- Selkoe DJ. Alzheimer’s disease: genes, proteins, and therapy. Physiol Rev. 2001; 81: 741-766.
- Giacobini E. Cholinesterase inhibitors: new roles and therapeutic alternatives. Pharmacol Res. 2004; 5: 433-440.
- Asadipour A, Alipour M, Jafari M, Khoobi M, Emami S, Nadri H, Sakhteman A, Moradi A, Sheibani V, Moghadam FH, Shafiee A, Foroumadi A. Novel coumarin-3-carboxamides bearing N-benzylpiperidine moiety as potent acetylcholinesterase inhibitors. Eur J Med Chem. 2013; 70: 623-630.
- Siddiqui N, Arshad MF, Ahsan W, Alam MS. Thiazoles: a valuable insight into the recent advances and biological activities. Int J Pharm Sci Drug Res. 2009; 1: 136-143.
- Mustafa SM, Naira VA, Chittoorb JP, Krishnapillaic S. Synthesis of 1,2,4-triazoles and thiazoles from thiosemicarbazide and its derivatives. Mini-Rev Org Chem. 2004;1: 375-385.
- Andreani A, Burnelli S, Granaiola M, Guardigli M, Leoni A, Locatelli A, Morigi R, Rambaldi M, Rizzoli M, Varoli L, Roda A. Chemiluminescent high-throughput microassay applied to imidazo [2,1-b]thiazole derivatives as potential acetylcholinesterase and butyrylcholinesterase inhibitors. Eur J Med Chem. 2008;43: 657-661. Sengupta AK, Garg M. New 5-arylamino-2[N-(2’mercaptoacetylamino-4’-arylthiazolo)]thiadiazoles(III): as AChE inhibitors. J Indian Chem Soc. 1980;57: 1241-1243.
- Shaw FH, Bentley GA. The pharmacology of some new anticholinesterases. Aust J Exp Biol Med Sci. 1953;31: 573–576.
- Matsunaga Y, Tanaka T, Yoshinaga K, Ueki S, Hori Y, Eta R. Acotiamide hydrochloride (Z-338), a new selective acetylcholinesterase inhibitor, enhances gastric motility without prolonging QT interval in dogs: comparison with cisapride, itopride, and mosapride. J Pharmacol Exp Ther. 2011;336: 791-800.
Details
| Primary Language | Turkish |
|---|---|
| Journal Section | Articles |
| Authors | |
| Publication Date | April 25, 2014 |
| Submission Date | April 25, 2014 |
| Published in Issue | Year 2014 Volume: 4 Issue: 1 |
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