Synthesis of novel tellurides bearing benzensulfonamide moiety as carbonic anhydrase inhibitors with antitumor activity

We have synthetized a novel series of beta-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 beta-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 mu M, but their efficacy decreased in hypoxic conditions reaching the 50% of the tumor cell viability only at 30 mu M. 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. (C) 2019 Elsevier Masson SAS. All rights reserved.