The synthesis and evaluation of anti-acetylcholinesterase activity of some 4(3H)-quinazolinone derivatives bearing substituted 1,3,4- thiadiazole

Year 2017, Volume: 21 Issue: 1, 96 - 101, 09.09.2016

Mine Uraz Sevgi Karakuş , Usama Abu Mohsen Zafer Asım Kaplancıklı , Sevim Rollas

https://doi.org/10.12991/marupj.259886

Abstract

In the present study, a series of 4(3H)-quinazolinone derivatives (5a-f) were synthesized through the cylization reaction of substituted 1,3,4-thiadiazoles containing an aromatic primary amin and anthranilic acid in the presence of acetic anhydride and acetic acid.  The structures of the synthesized compounds were confirmed by elemental analysis (C,H,N,S), IR, ¹H-NMR and mass spectroscopic (5b and 5f) methods. Each derivative was evaluated for its ability to inhibit acetylcholinesterase (AChE) using a modification of Ellman’s spectrophotometric method. Compounds 2-methyl-3-{4-[5-(ethylamino)-1,3,4-thiadiazol-2-yl]phenyl}quinazolin-4(3H)-one (5b) and 2-methyl-3-{4-[5-(cyclohexylamino)-1,3,4-thiadiazol-2-yl]phenyl}quinazolin-4(3H)-one (5d) can be identified as promising anticholinesterase agents due to their inhibitory effect when compared with Donepezil                  (IC₅₀ =0.054±0.002 μM) as a reference drug.

 

 

 

 

Keywords

4(3H)-Quinazolinone, 1, 3, 4-thiadiazole, antiacetylcholinesterase activity

1,3,4-Tiyadiazol içeren bazı 4(3H)-kinazolinon türevlerinin sentezi ve anti-asetilkolinesteraz aktiviteleri

Abstract

Bu çalışmada, aromatik pirimer
amin içeren sübstitüe  1,3,4-tiyadiazoller
ile antranilik asitin asetik asit ve asetik 
anhidritli ortamdaki siklizasyonundan bir seri 4(3H)-  kinazolinon türevi (5a-f) sentez edildi.
Bileşiklerin yapıları  IR, 1H-NMR, kütle
spektroskopisi (5b ve 5f) ve elementel  analiz
yöntemleri kullanılarak aydınlatıldı. Bileşiklerin aktivite  tayini Ellman’ın modifiye edilmiş
spektrofotometrik yöntemi  kullanılarak
yapıldı. Donepezil standardı ile karşılaştırıldığında  bileşik 5b (2-metil-3-{4-[5-(etilamino)-1,3,4-tiyadiazol-2-il]  fenil}kinazolin-4(3H)-on) ve bileşik 5d
(2-metil-3-{4-[5-  (siklohegzilamino)-1,3,4-tiyadiazol-2-il]fenil}kinazolin-4(3H)-  on) inhibitör etkilerine göre
antikolinesteraz ajanları olarak  tanımlanabilirler.  

Keywords

4(3H)-Kinazolinon, 1, 3, 4-tiyadiazol, antiasetilkolinesteraz aktivite

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