title: The Antileishmanial Potential of C-3 Functionalized Isobenzofuranones against Leishmania (Leishmania) Infantum Chagasi.
abstract: Leishmaniases are diseases caused by protozoan parasites of the genus Leishmania. Clinically, leishmaniases range from cutaneous to visceral forms, with estimated global incidences of 1.2 and 0.4 million cases per year, respectively. The treatment of these diseases relies on multiple parenteral injections with pentavalent antimonials or amphotericin B. However, these pharmaceuticals are either too toxic or expensive for routine use in developing countries. These facts call for safer, cheaper, and more effective new antileishmanial drugs. In this investigation, we describe the results of the assessment of the activities of a series of isobenzofuran-1(3H)-ones (phtalides) against Leishmania (Leishmania) infantum chagasi, which is the main causative agent of visceral leishmaniasis in the New World. The compounds were tested at concentrations of 100, 75, 50, 25 and 6.25 µM over 24, 48, and 72 h. After 48 h of treatment at the 100 µM concentration, compounds 7 and 8 decreased parasite viability to 4% and 6%, respectively. The concentration that gives half-maximal responses (LC50) for the antileishmanial activities of compounds 7 and 8 against promastigotes after 24 h were 60.48 and 65.93 µM, respectively. Additionally, compounds 7 and 8 significantly reduced parasite infection in macrophages.
authors.affiliation: Departamento de Química, Universidade Federal de Viçosa, Av. P.H. Rolfs, S/N, Viçosa, MG, 36.570-900, Brazil. wagner.pereira@ufv.br.
authors.forename: Wagner Luiz
authors.initials: WL
authors.lastname: Pereira
authors.affiliation: Departamento de Biologia Geral, Universidade Federal de Viçosa, Av. P.H. Rolfs, S/N, Viçosa, MG, 36.570-900, Brazil. raphael.biomed@gmail.com.|Instituto Nacional de Biotecnologia Estrutural e Química Medicinal em Doenças Infecciosas (INBEQMeDi), Instituto de Física de São Carlos, Av. Trabalhador São Carlense, 400, Caixa Postal 369, São Carlos, SP, 13.560-970, Brazil. raphael.biomed@gmail.com.
authors.forename: Raphael
authors.initials: R
authors.lastname: de Souza Vasconcellos
authors.affiliation: Departamento de Biologia Geral, Universidade Federal de Viçosa, Av. P.H. Rolfs, S/N, Viçosa, MG, 36.570-900, Brazil. chrismariotini@yahoo.com.br.|Instituto Nacional de Biotecnologia Estrutural e Química Medicinal em Doenças Infecciosas (INBEQMeDi), Instituto de Física de São Carlos, Av. Trabalhador São Carlense, 400, Caixa Postal 369, São Carlos, SP, 13.560-970, Brazil. chrismariotini@yahoo.com.br.
authors.forename: Christiane
authors.initials: C
authors.lastname: Mariotini-Moura
authors.affiliation: Departamento de Ciências Biológicas, Instituto de Ciências Exatas e Biológicas-ICEB/NUPEB, Campus do Morro do Cruzeiro, Universidade Federal de Ouro Preto, Ouro Preto, MG, 35.400-000, Brazil. rodrigosaar@nupeb.ufop.br.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Saar Gomes
authors.affiliation: Departamento de Biologia Geral, Universidade Federal de Viçosa, Av. P.H. Rolfs, S/N, Viçosa, MG, 36.570-900, Brazil. rafaelacfirmino@gmail.com.|Instituto Nacional de Biotecnologia Estrutural e Química Medicinal em Doenças Infecciosas (INBEQMeDi), Instituto de Física de São Carlos, Av. Trabalhador São Carlense, 400, Caixa Postal 369, São Carlos, SP, 13.560-970, Brazil. rafaelacfirmino@gmail.com.
authors.forename: Rafaela de Cássia
authors.initials: Rde C
authors.lastname: Firmino
authors.affiliation: Departamento de Química, Universidade Federal de Viçosa, Av. P.H. Rolfs, S/N, Viçosa, MG, 36.570-900, Brazil. adalbert31@hotmail.com.
authors.forename: Adalberto Manoel
authors.initials: AM
authors.lastname: da Silva
authors.affiliation: Departamento de Veterinária, Universidade Federal de Viçosa, Av. P.H. Rolfs, S/N, Viçosa, MG, 36.570-900, Brazil. aberlardo.junior@ufv.br.
authors.forename: Abelardo
authors.initials: A
authors.lastname: Silva Júnior
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Av. P.H. Rolfs, S/N, Viçosa, MG, 36.570-900, Brazil. gustavo.bressan@ufv.br.
authors.forename: Gustavo Costa
authors.initials: GC
authors.lastname: Bressan
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Av. P.H. Rolfs, S/N, Viçosa, MG, 36.570-900, Brazil. marcia@ufv.br.
authors.forename: Márcia Rogéria
authors.initials: MR
authors.lastname: Almeida
authors.affiliation: Departamento de Ciências Biológicas, Instituto de Ciências Exatas e Biológicas-ICEB/NUPEB, Campus do Morro do Cruzeiro, Universidade Federal de Ouro Preto, Ouro Preto, MG, 35.400-000, Brazil. afonso@nupeb.ufop.br.
authors.forename: Luís Carlos
authors.initials: LC
authors.lastname: Crocco Afonso
authors.affiliation: Departamento de Química, Universidade Federal de Viçosa, Av. P.H. Rolfs, S/N, Viçosa, MG, 36.570-900, Brazil. robsonr.teixeira@ufv.br.
authors.forename: Róbson Ricardo
authors.initials: RR
authors.lastname: Teixeira
authors.affiliation: Instituto Nacional de Biotecnologia Estrutural e Química Medicinal em Doenças Infecciosas (INBEQMeDi), Instituto de Física de São Carlos, Av. Trabalhador São Carlense, 400, Caixa Postal 369, São Carlos, SP, 13.560-970, Brazil. jufietto@ufv.br.|Departamento de Bioquímica e Biologia Molecular, Av. P.H. Rolfs, S/N, Viçosa, MG, 36.570-900, Brazil. jufietto@ufv.br.
authors.forename: Juliana
authors.initials: J
authors.lastname: Lopes Rangel Fietto
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D001572:Benzofurans / Q000494:pharmacology*; D002470:Cell Survival; D004353:Drug Evaluation, Preclinical; D018314:Leishmania infantum / Q000187:drug effects*; D007896:Leishmaniasis / Q000188:drug therapy; D008264:Macrophages / Q000187:drug effects / Q000469:parasitology; D051379:Mice; D000067996:RAW 264.7 Cells
chemical_list: D000981:Antiprotozoal Agents; D001572:Benzofurans
keywords: Leishmania (L.) infantum chagasi; in vitro leishmanicidal activity; isobenzofuranones; phthalides; visceral leishmaniasis