Indole-Based Hydrazones Containing A Sulfonamide Moiety as Selective Inhibitors of Tumor-Associated Human Carbonic Anhydrase Isoforms IX and XII

被引：23

作者：

Demir-Yazici, Kubra ^{[1
]}

Bua, Silvia ^{[2
]}

Akgunes, Nurgul Mutlu ^{[1
]}

Akdemir, Atilla ^{[3
]}

Supuran, Claudiu T. ^{[2
]}

Guzel-Akdemir, Ozlen ^{[1
]}

机构：

[1] Istanbul Univ, Dept Pharmaceut Chem, Fac Pharm, TR-34116 Istanbul, Turkey

[2] Univ Firenze, Dept NEUROFARBA, Sez Sci Farmaceut, I-50019 Florence, Italy

[3] Bezmialem Vakif Univ, Dept Pharmacol, Comp Aided Drug Discovery Lab, Fac Pharm, TR-34093 Istanbul, Turkey

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2019年 / 20卷 / 09期

关键词：

carbonic anhydrase; sulfonamides; hydrazones; enzyme inhibition; molecular modeling; MAMMALIAN ISOFORMS; DRUG DISCOVERY; DESIGN; SOLUBILITY; PATENT;

D O I：

10.3390/ijms20092354

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Novel sulfonamidoindole-based hydrazones with a 2-(hydrazinocarbonyl)-3-phenyl-1H-indole-5-sulfonamide scaffold were synthesized and tested in enzyme inhibition assays against the tumor-associated carbonic anhydrase isoforms, hCA IX and XII, and the off-targets, hCA I and II. The compounds showed selectivity against hCA IX and XII over hCA I and II. Six compounds showed K-I values lower than 10 nM against hCA IX or XII. Molecular modeling studies were performed to suggest binding interactions between the ligand and the hCA active sites.

引用

页数：14

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