Synthesis and Biological Evaluation of Imidazo[2,1-b]Thiazole based Sulfonyl Piperazines as Novel Carbonic Anhydrase II Inhibitors

Metabolites

Mallika Alvala¹  Sravya Pujitha¹  KesariLakshmi Manasa¹  Mohammed Arifuddin¹  Aaftaab Sethi¹  Andrea Angeli²  ClaudiuT. Supuran² 

[1] Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India;Neurofarba Dept., Università degli Studi di Firenze, Sezione di Scienze Farmaceutiche e Nutraceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence, Italy;

关键词: carbonic anhydrase;    hCA I;    hCA II;    hCA IX;    hCA XII;    imidazo[2,1-b]thiazole;   

DOI  :  10.3390/metabo10040136

来源: DOAJ

【 摘 要 】

A novel series of imidazo[2,1-b]thiazole-sulfonyl piperazine conjugates (9aa-ee) has been synthesized and evaluated for carbonic anhydrase (CA, EC 4.2.1.1) inhibitory potency against four isoforms: The cytosolic isozyme hCA I, II and trans-membrane tumor-associated isoform hCA IX and hCA XII, taking acetazolamide (AAZ) as standard drug, using a stopped flow CO₂ hydrase assay. The results revealed that most of the compounds showed selective activity against hCA II whereas none of them were active against hCA I, IX, XII (K_i > 100 µM). The physiologically dominant cytosolic isoform hCA II was inhibited by these molecules with inhibition constants in the range of 57.7–98.2 µM. This new derivative, thus, selectively inhibits hCA II over the hCA I, IX, XII isoforms, which may be used for further understanding the physiological roles of some of these isoforms in various pathologies.

【 授权许可】

Unknown