SEVDA TÜRK, FATİH TOK, HÜLYA ÇELİK, SEVGİ KARAKUŞ, HAYRUNNİSA NADAROĞLU, Bedia KOÇYİĞİT KAYMAKÇIOĞLU, KAAN KÜÇÜKOĞLU

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

In the present study, N-(5-methyl-1,3,4-thiadiazol-2-yl)4-[(3-substituted)ureido]benzenesulfonamide (1-9) and N-(5-methyl-1,3,4-thiadiazol-2-yl)-4-[(3-substituted) 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 0.144-15.65 nM) and CA II (IC50 values 0.10917.95 nM) in comparison with the clinically used CA inhibitor acetazolamide.

Karbonik anhidraz I ve II inhibitörü olan bazı N-(5-metil1,3,4-tiyadiazol-2-il)-4-[(3-sübstitüe)üreido/tiyoüreido] benzensülfonamitler

Bu çalışmada N-(5-metil-1,3,4-tiyadiazol-2-il)-4-[(3-sübstitüe) üreido]benzensülfonamit ve N-(5-metil-1,3,4-tiyadiazol-2il)-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.

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