We report for the first time a novel series of tellurides bearing sulfonamide as selective and potent inhibitors of the β-class carbonic anhydrase (CA; EC 4.2.1.1) enzyme expressed in Leishmania donovani protozoa. Such derivatives showed high activity against axenic amastigotes, and among them, compound 5g (4-(((3,4,5-trimethoxyphenyl)tellanyl)methyl)benzenesulfonamide) showed an IC50 of 0.02 μM being highly selective for the parasites over THP-1 cells with a selectivity index of 300. The in vitro and in vivo toxicity experiments showed compound 5g to possess a safe profile and thus paving the way for tellurium-containing compounds as novel drug entities.

Tellurides Bearing Sulfonamides as Novel Inhibitors of Leishmanial Carbonic Anhydrase with Potent Antileishmanial Activity / Angeli, Andrea; Etxebeste-Mitxeltorena, Mikel; Sanmartín, Carmen; Espuelas, Socorro; Moreno, Esther; Azqueta, Amaya; Parkkila, Seppo; Carta, Fabrizio; Supuran, Claudiu T. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - ELETTRONICO. - 63:(2020), pp. 4306-4314. [10.1021/acs.jmedchem.0c00211]

Tellurides Bearing Sulfonamides as Novel Inhibitors of Leishmanial Carbonic Anhydrase with Potent Antileishmanial Activity

Angeli, Andrea
;
Carta, Fabrizio;Supuran, Claudiu T
2020

Abstract

We report for the first time a novel series of tellurides bearing sulfonamide as selective and potent inhibitors of the β-class carbonic anhydrase (CA; EC 4.2.1.1) enzyme expressed in Leishmania donovani protozoa. Such derivatives showed high activity against axenic amastigotes, and among them, compound 5g (4-(((3,4,5-trimethoxyphenyl)tellanyl)methyl)benzenesulfonamide) showed an IC50 of 0.02 μM being highly selective for the parasites over THP-1 cells with a selectivity index of 300. The in vitro and in vivo toxicity experiments showed compound 5g to possess a safe profile and thus paving the way for tellurium-containing compounds as novel drug entities.
2020
63
4306
4314
Angeli, Andrea; Etxebeste-Mitxeltorena, Mikel; Sanmartín, Carmen; Espuelas, Socorro; Moreno, Esther; Azqueta, Amaya; Parkkila, Seppo; Carta, Fabrizio;...espandi
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1330313
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