N-Acylbenzenesulfonamide Dihydro-1,3,4-oxadiazole Hybrids: Seeking Selectivity toward Carbonic Anhydrase Isoforms

被引：26

作者：

Bianco, Giulia ^{[1
]}

Meleddu, Rita ^{[1
]}

Distinto, Simona ^{[1
]}

Cottiglia, Filippo ^{[1
]}

Gaspari, Marco ^{[2
]}

Melis, Claudia ^{[1
]}

Corona, Angela ^{[1
]}

Angius, Rossella ^{[3
]}

Angeli, Andrea ^{[4
]}

Taverna, Domenico ^{[2
]}

Alcaro, Stefano ^{[5
]}

Leitans, Janis ^{[6
]}

Kazaks, Andris ^{[6
]}

Tars, Kaspars ^{[6
]}

Supuran, Claudiu T. ^{[4
]}

Maccioni, Elias ^{[1
]}

机构：

[1] Univ Cagliari, Dept Life & Environm Sci, Via Osped 72, I-09124 Cagliari, Italy

[2] Magna Graecia Univ Catanzaro, Dept Expt & Clin Med, I-88100 Catanzaro, Italy

[3] Sardegna Ric, Lab NMR & Tecnol Bioanalit, I-09010 Pula, CA, Italy

[4] Univ Firenze, Sez Sci Farmaceut, Dipartimento NEUROFARBA, Florence, Italy

[5] Magna Graecia Univ Catanzaro, Dipartimento Sci Salute, Campus S Venuta,Viale Europa, I-88100 Catanzaro, Italy

[6] Latvian Biomed Res & Study Ctr, Ratsupites 1, Riga, Latvia

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2017年 / 8卷 / 08期

关键词：

human carbonic anhydrase; hCA; N-acylbenzenesulfonamide; 1,3,4-oxadiazole; hybrids; docking; SECONDARY SULFONAMIDES; BREAST-CANCER; ACTIVE-SITE; INHIBITORS; XII; DESIGN; IX; ACTIVATORS; SCAFFOLD; CELLS;

D O I：

10.1021/acsmedchemlett.7b00205

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of N-acylbenzenesulfonamide dihydro1,3,4-oxadiazole hybrids (EMAC8000(a-m)) was designed and synthesized with the aim to target tumor associated carbonic anhydrase (hCA) isoforms IX and XII. Most of the compounds were selective inhibitors of the tumor associated hCA XII. Moreover, resolution of EMAC8000d racemic mixture led to the isolation of the levorotatory eutomer exhibiting an increase of hCA XII inhibition potency and selectivity with respect to hCA II. Computational studies corroborated these data. Overall our data indicate that both substitution pattern and stereochemistry of dihydro-1,3,4-oxadiazole could be considered as key factors to determine activity and selectivity toward hCA isozymes. These results can provide further indication for the design and optimization of selective hCA inhibitors.

引用

页码：792 / 796

页数：5

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