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含有机金属酰腙配体的杂双金属配合物作为人碳酸酐酶潜在抑制剂。

Heterobimetallic complexes containing organometallic acylhydrazone ligands as potential inhibitors of human carbonic anhydrases.

机构信息

Facultad de Ciencias Químicas, Universidad de Concepción, Concepción, Chile.

Facultad de Ciencias Químicas, Universidad de Concepción, Concepción, Chile.

出版信息

J Inorg Biochem. 2022 Jul;232:111814. doi: 10.1016/j.jinorgbio.2022.111814. Epub 2022 Apr 5.

Abstract

In the search of new bioorganometallic compounds as potential inhibitors of human (h) carbonic anhydrases (hCAs, EC 4.2.1.1), heterobinuclear ruthenium(II) complexes based on organometallic-acylhydrazones have been obtained. The complexes (1a-b, 2a-b) were prepared by reaction between the corresponding organometallic-acylhydrazone of the general formula [{(η-CH)CH=N-NH-C(O)-CH-4-SONH}]MLn or [{(η-CH)CH=N-NH-C(O)-CHCH-NH-CH-4-SONH}]MLn (where MLn = Re(CO); FeCp) and [Ru(p-cymene)Cl]. All compounds were characterized by conventional spectroscopic techniques and cyclic voltammetry. Biological evaluation as CA inhibitors (CAIs) was carried out and showed derivatives 1a, 2a and 2b to behave as selective inhibition against the tumors associate isoforms hCA IX and XII making them interesting candidates for preclinical evaluation in various hypoxic tumors in which the two enzymes are overexpressed.

摘要

为了寻找新的生物有机金属化合物作为人源碳酸酐酶(hCA,EC 4.2.1.1)的潜在抑制剂,我们得到了基于有机金属酰腙的异双核钌(II)配合物。这些配合物(1a-b,2a-b)是通过相应的有机金属酰腙[{(η-CH)CH=N-NH-C(O)-CH-4-SONH}]MLn 或 [{(η-CH)CH=N-NH-C(O)-CHCH-NH-CH-4-SONH}]MLn(其中 MLn=Re(CO);FeCp)与[Ru(p-cymene)Cl]之间的反应制备的。所有化合物均通过常规光谱技术和循环伏安法进行了表征。作为碳酸酐酶抑制剂(CAIs)的生物评价表明,衍生物 1a、2a 和 2b 对肿瘤相关同工酶 hCA IX 和 XII 表现出选择性抑制作用,这使它们成为各种缺氧肿瘤中临床前评估的候选药物,这些肿瘤中两种酶过度表达。

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