Discovery of New Selenoureido Analogues of 4-(4-Fluorophenylureido)benzenesulfonamide as Carbonic Anhydrase Inhibitors,ACS Medicinal Chemistry Letters

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Discovery of New Selenoureido Analogues of 4-(4-Fluorophenylureido)benzenesulfonamide as Carbonic Anhydrase Inhibitors
ACS Medicinal Chemistry Letters ( IF 3.5 ) Pub Date : 2017-08-14 00:00:00 , DOI: 10.1021/acsmedchemlett.7b00280
Andrea Angeli ₁ , Damiano Tanini ₂ , Thomas S. Peat ₃ , Lorenzo Di Cesare Mannelli ₄ , Gianluca Bartolucci ₁ , Antonella Capperucci ₂ , Carla Ghelardini ₄ , Claudiu T. Supuran ₁ , Fabrizio Carta ₁

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A series of benzenesulfonamides bearing selenourea moieties was obtained considering the ureido-sulfonamide SLC-0111, in Phase I clinical trials as antitumor agent, as a lead molecule. All compounds showed interesting inhibition potencies against the physiologically relevant human (h) carbonic anhydrase (hCAs, EC 4.2.1.1) isoforms I, II, IV, and IX. The most flexible analogues in the series 14–19 showed low nanomolar inhibition constants against hCA I, II, and IX. We assessed selected compounds on the in vitro antioxidant properties and binding modes and evaluated ex vivo human prostate (PC3), breast (MDA-MB-231), and colon-rectal (HT-29) cancer cell lines both in normoxic and hypoxic conditions.

中文翻译：

发现新的硒代脲基类似物的4-（4-氟苯基脲基）苯磺酰胺作为碳酸酐酶抑制剂。

在I期临床试验中，以脲基磺酰胺SLC-0111作为抗肿瘤剂，以铅分子的形式获得了一系列带有硒脲部分的苯磺酰胺。所有化合物均显示出对生理相关的人类（h）碳酸酐酶（hCAs，EC 4.2.1.1）同工型I，II，IV和IX的有趣抑制作用。在该系列中最灵活类似物14 - 19显示对HCA I，II，IX和低纳摩尔抑制常数。我们评估了在常氧和低氧条件下体外抗氧化剂特性和结合模式的选定化合物，并评估了离体人类前列腺癌（PC3），乳腺癌（MDA-MB-231）和结肠直肠癌（HT-29）癌细胞系。

更新日期：2017-08-14

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