乙酰唑胺的有机钌(II)配合物能强烈抑制人碳酸酐酶同工酶 I、II、IX 和 XII。
Organoruthenium(II) complexes of acetazolamide potently inhibit human carbonic anhydrase isoforms I, II, IX and XII.
机构信息
a Faculty of Chemistry and Chemical Technology , University of Ljubljana , Ljubljana , Slovenia.
b Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche e Nutraceutiche , Università degli Studi di Firenze , Florence , Italy.
出版信息
J Enzyme Inhib Med Chem. 2019 Dec;34(1):388-393. doi: 10.1080/14756366.2018.1547288.
Two acetazolamide (AAZ) complexes with ruthenium(II) η-p-cymene chloride were synthesised, characterised and tested for their inhibitory effects on several carbonic anhydrase (CA, EC 4.2.1.1) isoforms with pharmacological applications. Against human (h) isoform hCA I, the two complexes showed inhibition constants in the range of 8.5-23.4 nM (AAZ has a K of 250 nM), against hCA II of 0.48-4.2 nM, whereas against hCA IX of 0.63-3.8 nM and against hCA XII of 0.04-0.52 nM, respectively. These highly effective ruthenium acetazolamide derivatives against the tumour-associated CA isoforms IX and XII warrant further in vivo studies, in hypoxic tumours overexpressing these enzymes.
合成了两种含有钌（II）η-p-环戊二烯氯化物的乙酰唑胺（AAZ）配合物，并对其进行了表征，同时测试了它们对几种具有药理学应用的碳酸酐酶（CA，EC 4.2.1.1）同工酶的抑制作用。这两种配合物对人（h）同工酶 hCA I 的抑制常数在 8.5-23.4 nM 范围内（AAZ 的 K 为 250 nM），对 hCA II 的抑制常数在 0.48-4.2 nM 范围内，而对 hCA IX 的抑制常数在 0.63-3.8 nM 范围内，对 hCA XII 的抑制常数在 0.04-0.52 nM 范围内。这些针对肿瘤相关 CA 同工酶 IX 和 XII 的高效钌乙酰唑胺衍生物值得进一步在缺氧肿瘤中进行过表达这些酶的体内研究。
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