Synthesis of N′-phenyl-N-hydroxyureas and investigation of their inhibitory activities on human carbonic anhydrases

被引：11

作者：

Bozdag, Murat ^{[1
]}

Carta, Fabrizio ^{[2
]}

Angeli, Andrea ^{[2
]}

Osman, Sameh M. ^{[3
]}

Alasmary, Fatmah A. S. ^{[3
]}

AlOthman, Zeid ^{[3
]}

Supuran, Claudiu T. ^{[2
]}

机构：

[1] Univ Florence, Dipartimento Chim, Lab Chim Bioinorgan, Rm 188,Via Lastruccia 3, I-50019 Florence, Italy

[2] Univ Florence, Dipartimento Neurofarba, Sez Sci Farmaceut, Via U Schiff 6, I-50019 Florence, Italy

[3] King Saud Univ, Coll Sci, Dept Chem, Riyadh, Saudi Arabia

来源：

BIOORGANIC CHEMISTRY | 2018年 / 78卷

关键词：

Carbonic anhydrase; Inhibitor; N '-phenyl-N-hydroxyurea; Hypoxic tumors; LOWERING AROMATIC/HETEROCYCLIC SULFONAMIDES; THERAPEUTIC APPLICATIONS; ANTIGLAUCOMA ACTION; NATURAL-PRODUCTS; IN-VIVO; BINDING; IX; DISCOVERY; POTENT; SERIES;

D O I：

10.1016/j.bioorg.2018.02.029

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：

A series of N'-phenyl-N-hydroxyureas has been prepared by reacting hydroxylamine with aromatic isocyanates. These compounds were investigated as inhibitors of human carbonic anhydrases (hCAs, EC 4.2.1.1), considering four physiologically relevant isoforms, the cytosolic isoforms hCA I and II, and tumor associated, transmembrane isoforms hCA IX and XII. The new compounds reported here did not inhibit the widespread cytosolic isoforms hCA I and II, but they inhibited the tumor associated isoforms with interesting potencies. The most effective inhibitors showed K(I)s ranging between 72.8 and 78.9 nM against hCA IX and between 6.9 and 7.2 against hCA XII, making them of interest as candidates for antitumor studies. (C) 2018 Elsevier Inc. All rights reserved.

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页码：1 / 6

页数：6

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