Some N-(5-methyl-1,3,4-thiadiazol-2-yl)-4-[(3-substituted) ureido/thioureido]benzenesulfonamides as carbonic anhydrase I and II inhibitors

Year 2017, Volume: 21 Issue: 1, 89 - 95, 25.08.2016

Sevda Türk Fatih Tok Hülya Çelik , Sevgi Karakuş , Hayrunnisa Nadaroğlu Bedia Koçyiğit-kaymakçıoğlu , Kaan Küçükoğlu

https://doi.org/10.12991/marupj.259885

Abstract

In the present study, N-(5-methyl-1,3,4-thiadiazol-2-yl)-4-[(3-substitue)ureido] benzenesulfonamide (1-9) and N-(5-methyl-1,3,4-thiadiazol-2-yl)-4-[(3-substitue) thioureido]benzenesulfonamide (10-14) derivatives were synthesized from 4-amino-N-(5-methyl-1,3,4-thiadiazol-2-yl)benzenesulfonamide (Sulfamethizole). All new compounds were characterized by elemental analysis and various spectroscopic methods (FTIR, ¹H-NMR and MS). These new sulfonamide derivatives were investigated as inhibitors of carbonic anhydrase especially human carbonic anhydrase I and II. The new compounds showed higher activity against the human cytosolic CA I (IC₅₀ values 0.095-15.65 nM) and CA II            (IC₅₀ values 0.057-17.95 nM) in comparison with the clinically used CAI inhibitor acetazolamide.

Keywords

Carbonic anhydrase inhibitors, sulfonamide, sulfamethizole, urea and thiourea

Karbonik anhidraz I ve II inhibitörü olan bazı N-(5-metil- 1,3,4-tiyadiazol-2-il)-4-[(3-sübstitüe)üreido/tiyoüreido] benzensülfonamitler

Abstract

Bu çalışmada
N-(5-metil-1,3,4-tiyadiazol-2-il)-4-[(3-sübstitüe)  üreido]benzensülfonamit ve
N-(5-metil-1,3,4-tiyadiazol-2-  il)-4-[(3-sübstitüe)tiyoüreido]benzensülfonamit
türevleri  4-amino-N-(5-metil-1,3,4-tiyadiazol-2-il)benzensülfonamitten  (sülfametizol) hareketle sentez edildi. Bütün
yeni bileşiklerin  yapıları elemental
analiz ve çeşitli spektroskopik yöntemler 
(FTIR, 1H-NMR ve MS) yardımıyla aydınlatıldı. Bu yeni  sülfonamit türevlerinin, özellikle insan
karbonik anhidraz  I ve II olmak üzere, karbonik
anhidraz inhibitor etkileri  incelendi.
Bileşiklerin klinikte kullanılan asetazolamide kıyasla  insan sitozolik CA I (IC50 değerleri
0.144-15.65 nM) ve CA II  (IC50 değerleri
0.109-17.95 nM) inhibisyon değerleri ile daha 
yüksek aktivite gösterdikleri tespit edildi.  

Keywords

Karbonik anhidraz inhibitörleri, sülfonamit, sülfametizol, üre ve tiyoüre

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