title: The new pyrazolyltetrazole derivative MSN20 is effective via oral delivery against cutaneous leishmaniasis.
abstract: An orally delivered, safe and effective treatment for leishmaniasis is an unmet medical need. Azoles and the pyrazolylpyrimidine allopurinol present leishmanicidal activity, but their clinical efficacies are variable. Here, we describe the activity of the new pyrazolyltetrazole hybrid, 5-[5-amino-1-(4'-methoxyphenyl)1H-pyrazole-4-yl]1H-tetrazole (MSN20). MSN20 showed a 50% inhibitory concentration (IC50) of 22.3 μM against amastigotes of Leishmania amazonensis and reduced significantly the parasite load in infected mice, suggesting its utility as a lead compound for the development of an oral treatment for leishmaniasis.
authors.affiliation: Laboratório de Bioquímica de Tripanosomatídeos, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil.
authors.forename: Viviane Dos Santos
authors.initials: Vdos S
authors.lastname: Faiões
authors.affiliation: Laboratório de Síntese de Moléculas Bioativas, Instituto de Física e Química, UNIFEI, Itajubá, Minas Gerais, Brazil.
authors.forename: Maurício Silva
authors.initials: MS
authors.lastname: Dos Santos
authors.affiliation: Programa de Pós-Graduação em Química, Departamento de Química Orgânica, Instituto de Química, UFF, Niterói, Rio de Janeiro, Brazil.
authors.forename: Alice Maria Rolim
authors.initials: AM
authors.lastname: Bernardino
authors.affiliation: Laboratório de Bioquímica de Tripanosomatídeos, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil.
authors.forename: Edézio Ferreira
authors.initials: EF
authors.lastname: Cunha-Júnior
authors.affiliation: Laboratório de Bioquímica de Tripanosomatídeos, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil.
authors.forename: Marilene Marcuzzo do
authors.initials: MM
authors.lastname: Canto Cavalheiro
authors.affiliation: Laboratório de Bioquímica de Tripanosomatídeos, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil ects@ioc.fiocruz.br.
authors.forename: Eduardo Caio
authors.initials: EC
authors.lastname: Torres-Santos
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy*; D051379:Mice; D011720:Pyrazoles / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000737:chemistry*
chemical_list: D000981:Antiprotozoal Agents; D011720:Pyrazoles; D013777:Tetrazoles; C045574:1H-tetrazole; C031280:pyrazole
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