Metronidazole-coumarin conjugates and 3-cyano-7-hydroxy-coumarin act as isoform-selective carbonic anhydrase inhibitors

被引：89

作者：

Bonneau, Adeline ^{[1
]}

Maresca, Alfonso ^{[2
]}

Winum, Jean-Yves ^{[1
]}

Supuran, Claudiu T. ^{[2
]}

机构：

[1] Ecole Natl Super Chim Montpellier, CNRS, UMR 5247, IBMM,UM1,UM2, Montpellier, France

[2] Univ Florence, Lab Chim Bioinorgan, Florence, Italy

来源：

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY | 2013年 / 28卷 / 02期

关键词：

Carbonic anhydrase; coumarin; nitroazole; metronidazole; enzyme inhibitor; monocarboxylate transporter; THERAPEUTIC APPLICATIONS; HYPOXIA; TUMORS; IX; ACTIVATORS; MARKERS; GROWTH; XII;

D O I：

10.3109/14756366.2011.650692

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Reaction of 6-/7-hydroxycoumarin with metronidazole afforded conjugates which incorporate two interesting chemotypes which may inhibit carbonic anhydrases (CAs, EC 4.2.1.1) due to the presence of the coumarin moiety and possess radiosensitizing effects due to the presence of the nitroazole. Another dual action compound, which may act both as CA inhibitor as well as monocarboxylate transporter inhibitor, is 3-cyano-7-hydroxy-coumarin. These compounds have been investigated as inhibitors of 11 human CA isoforms. Submicromolar inhibition was observed against hCA VA, hCA VB, hCA VI, hCA VII, hCA IX, hCA XII and hCA XIV, whereas isoforms hCA I, II and XIII were not inhibited by these compounds. These coumarins thus act as isoform-selective CA inhibitors with the possibility to target isoforms involved in pathologies such as obesity (CA VA/VB) or cancer (CA IX and XII) without inhibiting the physiologically dominant, highly abundant hCA I and II.

引用

页码：397 / 401

页数：5

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