Appraisal of anti-protozoan activity of nitroaromatic benzenesulfonamides inhibiting carbonic anhydrases from Trypanosoma cruzi and Leishmania donovani

Alessio Nocentini; Sameh M Osman; Igor A Almeida; Veronica Cardoso; Fatmah Ali S Alasmary; Zeid AlOthman; Alane B Vermelho; Paola Gratteri; Claudiu T Supuran

doi:10.1080/14756366.2019.1626375

Appraisal of anti-protozoan activity of nitroaromatic benzenesulfonamides inhibiting carbonic anhydrases from Trypanosoma cruzi and Leishmania donovani

J Enzyme Inhib Med Chem. 2019 Dec;34(1):1164-1171. doi: 10.1080/14756366.2019.1626375.

Authors

Alessio Nocentini¹, Sameh M Osman², Igor A Almeida³, Veronica Cardoso⁴, Fatmah Ali S Alasmary², Zeid AlOthman², Alane B Vermelho⁴, Paola Gratteri¹, Claudiu T Supuran¹

Affiliations

¹ a Department of Neuroscience, Psychology, Drug Research and Child's Health, Section of Pharmaceutical and Nutraceutical Sciences , University of Florence , Sesto Fiorentino , Italy.
² b Department of Chemistry, College of Science , King Saud University , Riyadh , Saudi Arabia.
³ c Department of Natural Products and Food, School of Pharmacy , Federal University of Rio de Janeiro , Rio de Janeiro , Brazil.
⁴ d BIOINOVAR - Biotechnology Laboratories: Biocatalysis, Bioproducts and Bioenergy, Institute of Microbiology Paulo de Góes , Federal University of Rio de Janeiro , Rio de Janeiro , Brazil.

Abstract

Chagas disease and leishmaniasis are neglected tropical disorders caused by the protozoans Trypanosoma cruzi and Leishmania spp. Carbonic anhydrases (CAs, EC 4.2.1.1) from these protozoans (α-TcCA and β-LdcCA) have been validated as promising targets for chemotherapic interventions. Many anti-protozoan agents, such as nitroimidazoles, nifurtimox, and benznidazole possess a nitro aromatic group in their structure which is crucial for their activity. As a continuation of our previous work on N-nitrosulfonamides as anti-protozoan agents, we investigated benzenesulfonamides bearing a nitro aromatic moiety against TcCA and LdcCA, observing selective inhibitions over human off-target CAs. Selected derivatives were assessed in vitro in different developmental stages of T. cruzi and Leishmania spp. A lack of significant growth inhibition has been found, which has been connected to the low permeability of this class of derivatives through cell membranes. Further strategies necessarily need to be designed for targeting Chagas disease and leishmaniasis with nitro-containing CA inhibitors.

Keywords: Carbonic anhydrase; Chagas disease; nitroaromatics.

MeSH terms

Antiprotozoal Agents / chemical synthesis
Antiprotozoal Agents / chemistry
Antiprotozoal Agents / pharmacology*
Carbonic Anhydrase Inhibitors / chemical synthesis
Carbonic Anhydrase Inhibitors / chemistry
Carbonic Anhydrase Inhibitors / pharmacology*
Carbonic Anhydrases / metabolism*
Dose-Response Relationship, Drug
Humans
Isoenzymes / antagonists & inhibitors
Isoenzymes / metabolism
Leishmania donovani / drug effects*
Leishmania donovani / enzymology
Molecular Structure
Parasitic Sensitivity Tests
Structure-Activity Relationship
Trypanosoma cruzi / drug effects*
Trypanosoma cruzi / enzymology

Substances

Antiprotozoal Agents
Carbonic Anhydrase Inhibitors
Isoenzymes
Carbonic Anhydrases

Grants and funding

This work was financed in part by a DSFP Project to Profs. Z. AlOthman and C.T. Supuran from King Saud University, Riyadh, Saudi Arabia, by the Coordenação de Aperfeiçoamento Pessoal de Nível Superior-Brasil (CAPES), Grant Code 001, by grants from Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ, Ed. 124/2013; Ed. 15/2015), Brazil, and by Conselho Nacional de Desenvolvimento Científico e Tecnológico (MCTI-CNPq, produtividade em pesquisa 303265/2015-9), Brazil.