Jaydeo T. Kilbile, Suryakant B. Sapkal, Gioele Renzi, Ilaria D’Agostino, Luigi Cutarella, Mattia Mori, Barbara De Filippis, Imadul Islam, Maria Luisa Massardi, Elena Somenza, Roberto Ronca, Yasinalli Tamboli*, Fabrizio Carta* and Claudiu T. Supuran,
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引用次数: 0
Abstract
In this study, a focused library of oxime ester derivatives of 2,4-dichloro-5-sulfamoylbenzoic acid (lasamide) containing Schiff bases was synthesized and tested in vitro for their ability to inhibit the cytosolic human carbonic anhydrases (hCAs) I and II, as well as the transmembrane and tumor-associated IX and XII isoforms. As a result, we obtained a first line of knowledge on lasamide derivatives potentially useful for development as CA inhibitors (CAIs). In particular, we focused our attention on the derivative 11, which was selective toward hCAs IX and XII over the cytosolic isoenzymes. An in silico study was conducted to assess the binding mode of 11 within hCAs IX and XII. Also, antiproliferative assays highlighted promising derivatives. The data obtained in this study are currently in use for the development of better-performing compounds on the tumor-associated isoforms.
在这项研究中,我们合成了一个含有希夫碱的 2,4-二氯-5-氨基磺酰基苯甲酸(lasamide)肟酯衍生物重点库,并在体外测试了它们抑制细胞质人碳酸酐酶(hCA)I 和 II 以及跨膜和肿瘤相关的 IX 和 XII 异构体的能力。因此,我们对有可能用作 CA 抑制剂(CAIs)的 Lasamide 衍生物有了初步的了解。我们特别关注了衍生物 11,它对 hCA IX 和 XII 的选择性高于细胞同工酶。我们进行了一项硅学研究,以评估 11 在 hCA IX 和 XII 中的结合模式。此外,抗增殖试验也突显了有前景的衍生物。这项研究获得的数据目前正用于开发针对肿瘤相关同工酶的性能更好的化合物。