新型亚胺硫代唑烷苯磺酰胺的合成、生物评价及计算研究作为有效的碳酸酐酶 II 和 IX 抑制剂。
Synthesis, biological evaluation and computational studies of novel iminothiazolidinone benzenesulfonamides as potent carbonic anhydrase II and IX inhibitors.
机构信息
Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan.
Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan.
出版信息
Bioorg Chem. 2018 Apr;77:381-386. doi: 10.1016/j.bioorg.2018.01.031. Epub 2018 Jan 31.
A series of iminothiazolidinone-sulfonamide hybrids (2a-k) was synthesized by heterocyclization of sulfanilamide thioureas with methyl bromoacetate and characterized by spectroscopic techniques, mass and elemental analysis. The synthesized derivatives were screened against four relevant human (h) isoforms of carbonic anydrases (CAs, EC 4.2.1.1) I, II, IV and IX. These enzymes are involved in a variety of diseases, including glaucoma, retinitis pigmentosa, epilepsy, arthritis, and tumors. Derivatives 2a-2k exhibited the best inhibitory activity against the cytosolyc hCA II (Ks are reaching the sub-nanomolar range, 0.41-37.8 nM) and against the tumor-associated isoform hCA IX (Ks are spanning between 24.3 and 368.3 nM). The binding mode of the reported iminothiazolidinone benzenesulfonamides within hCA II and IX catalytic clefts was investigated by docking studies.
通过磺酰胺硫脲与溴乙酸甲酯的杂环化反应，合成了一系列亚胺噻唑烷-磺酰胺杂合化合物（2a-k），并通过光谱技术、质谱和元素分析进行了表征。将合成的衍生物进行了筛选，以评估它们对四种相关的人源碳酸酐酶（CA，EC 4.2.1.1）同工酶 I、II、IV 和 IX 的抑制活性。这些酶与多种疾病有关，包括青光眼、色素性视网膜炎、癫痫、关节炎和肿瘤。衍生物 2a-2k 对细胞质 hCA II（Ks 值达到亚纳摩尔范围，0.41-37.8 nM）和肿瘤相关同工酶 hCA IX（Ks 值在 24.3 和 368.3 nM 之间）表现出最佳的抑制活性。通过对接研究，研究了所报道的亚胺噻唑烷-苯磺酰胺在 hCA II 和 IX 催化裂缝中的结合模式。
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