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
  • 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.