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Here we report the synthesis of natural products (NPs) 5′- O -sulfamoyl adenosine 1 and 5′- O -sulfamoyl-2-chloroadenosine 2 . As primary sulfamates these compounds represent an uncommon class of NPs, furthermore there are few NPs known that contain a N S bond. Compounds 1 and 2 were evaluated for inhibition of carbonic anhydrases (CA), a metalloenzyme family where the primary sulfamate is known to coordinate to the active site zinc and form key hydrogen bonds with adjacent CA active site residues. Both NPs were good to moderate CA inhibitors, with compound 2 a 20–50-fold stronger CA inhibitor ( K i values 65–234 nM) than compound 1 . The protein X-ray crystal structures of 1 and 2 in complex with CA II show that it is not the halogen-hydrophobic interactions that give compound 2 a greater binding energy but a slight movement in orientation of the ribose ring that allows better hydrogen bonds to CA residues. Compounds 1 and 2 were further investigated for antimicrobial activity against a panel of microbes relevant to human health, including Gram-negative bacteria (4 strains), Gram-positive bacteria (1 strain) and yeast (2 strains). Antimicrobial activity and selectivity was observed. The minimum inhibitory concentration (MIC) of NP 1 was 10 µM against Gram-positive Staphylococcus aureus and NP 2 was 5 µM against Gram-negative Escherichia coli . This is the first time that NP primary sulfamates have been assessed for inhibition and binding to CAs, with systematic antimicrobial activity studies also reported. [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]