Studies on hydrazide–hydrazones derivatives as acetylcholinesterase inhibitors

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

Usame Abu Mohsen Bedia Koçyiğit Kaymakçıoğlu , Emine Elçin Oruç Emre Zafer Asım Kaplancıklı Sevim Rollas

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.

Keywords

Hydrazide, hydrazone, anti-acetylcholinesterase activity

Asetilkolin esteraz inhibitörü olan hidrazid hidrazonlar üzerinde çalışmalar

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.

Keywords

Hidrazit, hidrazon, anti-asetilkolinesteraz aktivite

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