Yusuf Özkay, Leyla Yurttaş, Usama Abu Mohsen, Belgin Sever, Weiam Hussein, Ömer Öztürk, Begüm Nurpelin Sağlık, Ulviye Acar, Özge Nurhan Erdoğan, Ayşen Pekbağ, Zafer Asım Kaplancıklı

Asetilkolinesteraz inhibitörü olarak tiyazolil-hidrazon türevleri üzerine çalışma

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.Anahtar Kelimeler : Tiyazol, hidrazon, pirol, antikolinesteraz aktivite

Anahtar Kelimeler:

Tiyazol, hidrazon, pirol, antikolinesteraz aktivite

Study on thiazolyl-hydrazone derivatives as acetylcholinesterase inhibitors

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.Key words: Thiazole, hydrazone, pyrrole, anticholinesterase activity

Keywords:

Thiazole, hydrazone, pyrrole, anticholinesterase activity,

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