Computational investigation of the selectivity of salen and tetrahydrosalen compounds towards the tumor-associated hCA XII isozyme

被引：44

作者：

Akdemir, Atilla ^{[1
]}

De Monte, Celeste ^{[2
]}

Carradori, Simone ^{[2
]}

Supuran, Claudiu T. ^{[3
,4
]}

机构：

[1] Bezmialem Vakif Univ, Fac Pharm, Dept Pharmacol, TR-34093 Istanbul, Turkey

[2] Univ Roma La Sapienza, Dept Drug Chem & Technol, I-00185 Rome, Italy

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

[4] Univ Florence, Neurofarba Dept, Sez Sci Farmaceut & Nutraceut, Florence, Italy

来源：

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY | 2015年 / 30卷 / 01期

关键词：

Carbonic anhydrase inhibitor; docking; salen; tetrahydrosalen; CARBONIC-ANHYDRASE INHIBITORS; I-XIV; SULFONAMIDES; PHENOLS;

D O I：

10.3109/14756366.2014.892936

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：

In previous work, 14 salen and tetrahydrosalen compounds have been synthesized and tested in enzyme inhibition assays against cytosolic human carbonic anhydrase isozymes I and II (hCA I and II) and tumor-associated isozymes IX and XII (hCA IX and XII). These compounds show selectivity against hCA XII over hCA I, II and IX. In this study, molecular modeling and docking studies were applied to understand this preference of the compounds for hCA XII. Most likely, the compounds can displace the zinc-bound water molecule of hCA XII to form a direct interaction with the Zn2+ ion. In the other isozymes, the compounds might not be able to displace the water molecule nor are they expected to interact with the Zn2+ ion.

引用

页码：114 / 118

页数：5

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