Synthesis and evaluation of new thiadiazole derivatives as potential inhibitors of human carbonic anhydrase isozymes (hCA-I and hCA-II)

被引：16

作者：

Altintop, Mehlika Dilek ^{[1
]}

Ozdemir, Ahmet ^{[1
]}

Kucukoglu, Kaan ^{[2
]}

Turan-Zitouni, Gulhan ^{[1
]}

Nadaroglu, Hayrunnisa ^{[3
]}

Kaplancikli, Zafer Asim ^{[1
,4
]}

机构：

[1] Anadolu Univ, Dept Pharmaceut Chem, Fac Pharm, TR-26470 Eskisehir, Turkey

[2] Ataturk Univ, Dept Pharmaceut Chem, Fac Pharm, Erzurum, Turkey

[3] Ataturk Univ, Dept Food Technol, Erzurum Vocat Training Sch, Erzurum, Turkey

[4] Anadolu Univ, Dept Pharmaceut Chem, Grad Sch Hlth Sci, TR-26470 Eskisehir, Turkey

来源：

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY | 2015年 / 30卷 / 01期

关键词：

Carbonic anhydrase; hydratase activity; thiadiazole; 5-AMINO-1,3,4-THIADIAZOLE-2-SULFONAMIDE DERIVATIVES; MEDICINAL CHEMISTRY; BOVINE STOMACH; PURIFICATION; ERYTHROCYTES; TARGETS; SERIES;

D O I：

10.3109/14756366.2013.873038

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

2-[[5-(2,4-Difluoro/dichlorophenylamino)-1,3,4-thiadiazol-2-yl]thio] acetophenone derivatives (3a-s) were designed as human carbonic anhydrase isozymes (hCA-I and hCA-II) inhibitors and synthesized. hCA-I and hCA-II were purified from erythrocyte cells by the affinity chromatography. The inhibitory effects of 18 newly synthesized acetophenones on hydratase activity of these isoenzymes were studied in vitro. The average IC50 values of the new compounds for hydratase activity ranged from 0.033 to 0.14 mu M for hCA-I and from 0.030 to 0.11 mu M for hCA-II. Among the newly synthesized compounds, 2-[[5-(2,4-dichlorophenylamino)-1,3,4- thiadiazol-2-yl] thio]-4'-bromoacetophenone (3n) can be considered as a promising hCA-II inhibitor owing to its selective and potent inhibitory effect on hCA-II.

引用

页码：32 / 37

页数：6

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