Center for Brain Technology, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, South Korea.
Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
J Enzyme Inhib Med Chem. 2023 Dec;38(1):2154603. doi: 10.1080/14756366.2022.2154603.
A series of 6-ureido/amidocoumarins ( and ) has been designed and synthesised to develop potent and isoform- selective carbonic anhydrase CA XI and XII inhibitors. All coumarin derivatives were investigated for their CA inhibitory effect against CA I, II, IX, and XII. Interestingly, target coumarins potently inhibited both tumour-related isoforms CA IX (s: 14.7-82.4 nM) and CA XII (s: 5.9-95.1 nM), whereas the cytosolic off-target CA I and II isoforms have not inhibited by all tested coumarins up to 100 μM. These findings granted the target coumarins an excellent selectivity profile towards both CA IX and CA XII isoforms, supporting their development as promising anticancer candidates. Moreover, all target molecules were evaluated for their anticancer activities against HCT-116 and MCF-7 cancer cells. The 3,5-bis-trifluoromethylphenyl ureidocoumarin , exerted the best anticancer activity. Overall, ureidocoumarins, particularly compound could serve as a promising prototype for the development of potent anticancer CAIs.
一系列 6-脒基/酰胺基香豆素（和）已被设计和合成，以开发有效的和同工型选择性碳酸酐酶 CA XI 和 XII 抑制剂。所有香豆素衍生物均针对 CA I、II、IX 和 XII 进行了 CA 抑制作用的研究。有趣的是，目标香豆素对肿瘤相关同工型 CA IX（s：14.7-82.4 nM）和 CA XII（s：5.9-95.1 nM）具有很强的抑制作用，而细胞质非靶标 CA I 和 II 同工型在高达 100 μM 时不受所有测试香豆素的抑制。这些发现赋予了目标香豆素对 CA IX 和 CA XII 同工型的优异选择性特征，支持它们作为有前途的抗癌候选物的发展。此外，所有目标分子都针对 HCT-116 和 MCF-7 癌细胞进行了抗癌活性评估。3,5-双三氟甲基苯甲脒基香豆素，表现出最佳的抗癌活性。总体而言，脒基香豆素，特别是化合物，可作为开发有效的抗癌 CAIs 的有前途的原型。
