Inhibition of carbonic anhydrases from the extremophilic bacteria Sulfurihydrogenibium yellostonense (SspCA) and S. azorense (SazCA) with a new series of sulfonamides incorporating aroylhydrazone-, [1,2,4]triazolo[3,4-b][1,3,4]thiadiazinyl- or 2-(cyanophenylmethylene)-1,3,4-thiadiazol-3(2H)-yl moieties
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- 作者：Ahmed M. Alafeefy ; Hatem A. Abdel-Aziz ; Daniela Vullo ; Abdul-Malek S. Al-Tamimi ; Nabila A. Al-Jaber ; Clemente Capasso ; Claudiu T. Supuran
- 关键词：Carbonic anhydrase ; Alpha-class enzyme ; Sulfonamide ; Sulfurihydrogenibium spp. ; Extremophiles ; Inhibition study
- 刊名：Bioorganic and Medicinal Chemistry
- 出版年：1 January, 2014
- 年：2014
- 卷：22
- 期：1
- 页码：141-147
- 全文大小：491 K
文摘
A series of new sulfonamides was prepared starting from 2-oxo-N鈥?/em>-(4-sulfamoylphenyl)-propanehydrazonoyl chloride, a sulfanilamide derivative, which was reacted with aroylhydrazides, amines, or thiols. A library of derivatives incorporating aroylhydrazone, [1,2,4]triazolo[3,4-b][1,3,4]thiadiazinyl- or 2-(cyanophenyl-methylene)-1,3,4-thiadiazol-3(2H)-yl moieties was thus synthesized. The new compounds were investigated as inhibitors of four 伪-carbonic anhydrases (CAs, EC 4.2.1.1), the human (h) isoforms hCA I and II, and the bacterial ones recently isolated from the extremophilic bacteria Sulfurihydrogenibium yellostonense (SspCA) and Sulfurihydrogenibium azorense (SazCA). Low nanomolar activity was observed against hCA II (KIs of 0.56-17.1 nM) whereas hCA I was less inhibited by these compounds (KIs of 86.4 nM-32.8 渭M). The bacterial CAs were also effectively inhibited by these derivatives (KIs in the range of 0.77-234 nM against SazCA, and of 6.2-89.1 against SspCA, respectively), with several low nanomolar/subnanomolar inhibitors detected against both of them. As SspCA and SazCA are among the most thermostable and catalytically active CAs, it is of interest to find modulators of their activity for potential biotechnologic applications.