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Sulphonamide inhibition studies of the β-carbonic anhydrase GsaCAβ present in the salmon platyhelminth parasite Gyrodactylus salaris

机译:鲑鱼扁形蠕虫寄生虫 Gyrodactylus salaris 中存在的 β-碳酸酐酶 GsaCAβ 的磺胺抑制研究

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摘要

A β-class carbonic anhydrase (CA, EC 4.2.1.1) present in the genome of the Monogenean platyhelminth Gyrodactylus salaris, a fish parasite, GsaCAβ, has been investigated for its inhibitory effects with a panel of sulphonamides and sulfamates, some of which in clinical use. Several effective GsaCAβ inhibitors were identified, belonging to simple heterocyclic sulphonamides, the deacetylated precursors of acetazolamide and methazolamide (KIsof 81.9–139.7 nM). Many other simple benezene sulphonamides and clinically used agents, such as acetazolamide, methazolamide, ethoxzolamide, dorzolamide, benzolamide, sulthiame and hydrochlorothiazide showed inhibition constants <1 µM. The least effective GsaCAβ inhibitors were 4,6-disubstituted-1,3-benzene disulfonamides, with KIs in the range of 16.9–24.8 µM. Although no potent GsaCAβ-selective inhibitors were detected so far, this preliminary investigation may be helpful for better understanding the inhibition profile of this parasite enzyme and for the potential development of more effective and eventually parasite-selective inhibitors.
机译:存在于单基因扁形蠕虫 Gyrodactylus salaris 基因组中的 β 类碳酸酐酶 (CA, EC 4.2.1.1),一种鱼类寄生虫 GsaCAβ,已经研究了其对一组磺胺类和氨基磺酸盐的抑制作用,其中一些用于临床。鉴定出几种有效的 GsaCAβ 抑制剂,属于简单的杂环磺酰胺,乙酰唑胺和甲唑胺的脱乙酰化前体 (KIsof 81.9–139.7 nM)。许多其他简单的苯磺酰胺类药物和临床使用的药物,如乙酰唑胺、甲唑胺、乙氧唑胺、多佐胺、苯甲酰胺、磺噻嗪和氢氯噻嗪显示出 <1 μM 的抑制常数。效果最差的 GsaCAβ 抑制剂是 4,6-二取代-1,3-苯二磺酰胺,KIs 在 16.9–24.8 μM 范围内。尽管到目前为止尚未检测到有效的 GsaCAβ 选择性抑制剂,但这项初步研究可能有助于更好地了解这种寄生虫酶的抑制特性,并可能有助于开发更有效且最终寄生虫选择性抑制剂。

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