2. Academic Validation
  3. Tellurides Bearing Sulfonamides as Novel Inhibitors of Leishmanial Carbonic Anhydrase with Potent Antileishmanial Activity

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

  • J Med Chem. 2020 Apr 23;63(8):4306-4314. doi: 10.1021/acs.jmedchem.0c00211.
Andrea Angeli 1 2,  Mikel Etxebeste-Mitxeltorena 3,  Carmen Sanmartín 3,  Socorro Espuelas 3,  Esther Moreno 3,  Amaya Azqueta 3,  Seppo Parkkila 4,  Fabrizio Carta 1,  Claudiu T Supuran 1
Affiliations

Affiliations

  • 1 NEUROFARBA Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, University of Florence, Via Ugo Schiff 6, Sesto Fiorentino, 50019 Florence, Italy.
  • 2 Centre of Advanced Research in Bionanoconjugates and Biopolymers Department, "Petru Poni" Institute of Macromolecular Chemistry, 700487 Iasi, Romania.
  • 3 School of Pharmacy and Nutrition, Department of Pharmaceutical Technology and Chemistry, University of Navarra, Irunlarrea 1, 31008 Pamplona, Spain.
  • 4 Faculty of Medicine and Life Sciences, University of Tampere and Fimlab Ltd, Tampere University Hospital, 33100 Tampere, Finland.
PMID: 32223141 DOI: 10.1021/acs.jmedchem.0c00211
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.

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