Mehmet Onyilmaz, Murat Koca, Andrea Ammara, Mustafa Degirmenci, Claudiu T Supuran
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引用次数: 0
Abstract
Aim: A series of isocoumarin-chalcone hybrids were prepared and assays for the inhibition of four isoforms of human carbonic anhydrase (hCA; EC 4.2.1.1), hCA I, II, IX and XII. Materials & methods: Isocoumarin-chalcone hybrids were synthesized by condensing acetyl-isocoumarin with aromatic aldehydes. They did not significantly inhibit off-target cytosolic isoforms hCA I and II (KI >100 μM) but acted as low micromolar or submicromolar inhibitors for the tumor-associated isoforms hCA IX and XII. Results & conclusion: Our work provides insights into a new and scarcely investigated chemotype which provides interesting tumor-associated CA inhibitors, considering that some such derivatives like sulfonamide SLC-0111 are in advanced clinical trials for the management of metastatic advanced solid tumors.
目的：制备一系列异香豆素-查尔酮混合物，并测定其对人碳酸酐酶（hCA；EC 4.2.1.1）四种同工酶（hCA I、II、IX 和 XII）的抑制作用。材料与方法异香豆素-查尔酮混合物是通过乙酰基异香豆素与芳香醛缩合合成的。它们对非靶细胞异构体 hCA I 和 II（KI >100 μM）没有明显的抑制作用，但对肿瘤相关异构体 hCA IX 和 XII 起到了低微摩尔或亚微摩尔抑制作用。结果与结论：考虑到磺酰胺 SLC-0111 等一些此类衍生物正处于治疗转移性晚期实体瘤的晚期临床试验阶段，我们的研究工作为一种新的、鲜有研究的化学类型提供了见解，这种化学类型提供了有趣的肿瘤相关 CA 抑制剂。
期刊介绍：
Future Medicinal Chemistry offers a forum for the rapid publication of original research and critical reviews of the latest milestones in the field. Strong emphasis is placed on ensuring that the journal stimulates awareness of issues that are anticipated to play an increasingly central role in influencing the future direction of pharmaceutical chemistry. Where relevant, contributions are also actively encouraged on areas as diverse as biotechnology, enzymology, green chemistry, genomics, immunology, materials science, neglected diseases and orphan drugs, pharmacogenomics, proteomics and toxicology.
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