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[Display omitted] We report for the first time a small series of compounds endowed in vitro with inhibitory properties for the human (h) expressed Carbonic Anhydrase (CAs, E.C. 4.2.1.1) enzymes of physiological interest (i.e. I, II, VA, IX and XII) and bearing the pyrazolo[1,5- a ]pyrimidine (PP) scaffold at the tail section. Among the series reported, 1a-3a , 7a , 8a , 1b and 2b resulted effective ligands and with good selectivities for the hCAs II, IX or XII. In consideration of the nearly matching K I values of 7a for both the hCA II and IX (i.e. 26.4 and 23.0 nM respectively) we explored its binding mode within the CA IX mimic isoform by means of X-ray crystal experiments on the corresponding adduct. [ABSTRACT FROM AUTHOR]

We have synthetized a novel series of β-hydroxy tellurides bearing the benzenesulfonamide group as potent inhibitors of carbonic anhydrase enzymes. In a one pot procedure, we discovered both the ring opening reaction of the three-membered ring and the cleavage of the sulfonamide protecting moiety at the same time. Moreover, the first X-ray co-crystallographic structure of a β-hydroxy telluride derivative with hCA II is reported. The potent effects of these compounds against the tumor-associated hCA IX with low nanomolar constant inhibition values give the possibility to evaluate their activity in vitro using a breast cancer cell line (MDA-MB-231). Compounds 7e and 7g induced significant toxic effects against tumor cells after 48 h incubation in normoxic conditions killing over 50% of tumor cells at 3 μM, but their efficacy decreased in hypoxic conditions reaching the 50% of the tumor cell viability only at 30 μM. These unusual features make them interesting lead compounds to act as antitumor agents, not only as Carbonic Anhydrase IX inhibitors, but reasonably in different pathways, where hCA IX is not overexpressed. Image 1 • Development of an easy procedure for the synthesis of novel β-hydroxy tellurides bearing the benzenesulfonamide moiety. • Evaluation of their inhibitory activity against hCAs I, II, IV, VII, IX. • Potent inhibitory activity was found against the tumor-associated hCA IX. • X-rays co-crystallographic studies. • Interesting activities were found in vitro against breast cancer cell line (MDA-MB-231). [ABSTRACT FROM AUTHOR]