Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana State, India.
Università degli Studi di Firenze, Neurofarba Dept., Sezione di Scienze Farmaceutiche e Nutraceutiche, Via Ugo Schiff 6, 50019, Sesto Fiorentino, Florence, Italy.
ChemMedChem. 2021 Apr 20;16(8):1252-1256. doi: 10.1002/cmdc.202000915. Epub 2021 Feb 9.
A series of coumarin-thiourea hybrids (4 a-o) has been synthesized, and the compounds have been evaluated against the tumour associated transmembrane isoform, human (h) carbonic anhydrase (CA) hCA IX and the less-explored cytosolic isoform, hCA XIII. All compounds exhibited potent inhibition of both isoforms, with K values of <100 nM against hCA IX. Compound 4 b was the best inhibitor (K =78.5 nM). All the compounds inhibited hCA XIII in the low-nanomolar to sub-micromolar range, with compound 4 b again showing the best inhibition (K =76.3 nM). With compound 4 b as a lead, more-selective inhibitors of hCA IX and hCA XIII or dual hCA IX/XIII inhibitors might be developed.
已经合成了一系列香豆素-硫脲杂合体（4a-o），并对其进行了评估，以针对肿瘤相关的跨膜同工型人（h）碳酸酐酶（CA）hCAIX 和探索较少的胞质同工型 hCAXIII。所有化合物均对两种同工酶表现出强烈的抑制作用，对 hCAIX 的 K 值<100nM。化合物 4b 是最好的抑制剂（K=78.5nM）。所有化合物均以低纳摩尔至亚微摩尔范围抑制 hCAXIII，化合物 4b 再次显示出最佳抑制作用（K=76.3nM）。以化合物 4b 为先导，可能会开发出对 hCAIX 和 hCAXIII 更具选择性的抑制剂或双重 hCAIX/XIII 抑制剂。
