Institute of Technology of Organic Chemistry, Faculty of Materials Science and Applied Chemistry, Riga Technical University, Riga, Latvia.
NEUROFARBA Department, Pharmaceutical and Nutraceutical Section, University of Florence, Florence, Italy.
J Enzyme Inhib Med Chem. 2023 Dec;38(1):2174981. doi: 10.1080/14756366.2023.2174981.
A small library of substituted cyclic guanidine incorporated benzothiazole-6-sulphonamides was synthesized. All obtained compounds were investigated for their inhibitory activity against the key brain-associated human carbonic anhydrase isoform hCA VII (a promising target for the treatment of neuropathic pain) and three isoforms expressed in brain and other tissues, hCA I, II, and IV. Sulphaguanidine derivatives were inactive on the all investigated isoforms while the primary sulphonamide containing guanidines and were inactive towards hCA IV but displayed inhibiting properties on hCA I, II, and VII with K values in the low nanomolar to micromolar ranges. The results indicated that isoforms hCA II and VII were potently and selectively inhibited by these compounds, whereas the cytosolic hCA I was less sensitive to inhibition. The derivatives reported in this study might be useful for design of more potent and selective inhibitors of hCA II and VII.
合成了一个包含取代环状胍的苯并噻唑-6-磺酰胺的小文库。所有获得的化合物都被研究了它们对关键脑相关人碳酸酐酶同工酶 hCA VII（治疗神经性疼痛的有希望的靶标）和在脑和其他组织中表达的三种同工酶 hCA I、II 和 IV 的抑制活性。磺胺胍衍生物对所有研究的同工酶均无活性，而含有胍的主要磺酰胺 和 对 hCA IV 无活性，但对 hCA I、II 和 VII 具有抑制特性，K 值在纳摩尔到微摩尔范围内。结果表明，这些化合物强烈且选择性地抑制同工酶 hCA II 和 VII，而细胞质 hCA I 对抑制的敏感性较低。本研究中报道的衍生物可能有助于设计更有效和选择性的 hCA II 和 VII 抑制剂。
