The Antileishmanial Potential of C-3 Functionalized Isobenzofuranones against Leishmania (Leishmania) Infantum Chagasi

Molecules

Wagner Luiz Pereira⁶  Raphael de Souza Vasconcellos¹  Christiane Mariotini-Moura¹  Rodrigo Saar Gomes⁴  Rafaela de Cássia Firmino¹  Adalberto Manoel da Silva⁶  Abelardo Silva Júnior²  Gustavo Costa Bressan⁵  Márcia Rogéria Almeida⁵  Luís Carlos Crocco Afonso⁴  R༻son Ricardo Teixeira⁶  Juliana Lopes Rangel Fietto³ 

[1] Departamento de Biologia Geral, Universidade Federal de Viçosa, Av. P.H. Rolfs, S/N, Viçosa, MG, 36.570-900, Brazil;Departamento de Veterinária, Universidade Federal de Viçosa, Av. P.H. Rolfs, S/N, Viçosa, MG, 36.570-900, Brazil;;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, BrazilDepartamento 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;Departamento de Bioquímica e Biologia Molecular, Av. P.H. Rolfs, S/N, Viçosa, MG, 36.570-900, Brazil;Departamento de Química, Universidade Federal de Viçosa, Av. P.H. Rolfs, S/N, Viçosa, MG, 36.570-900, Brazil;

关键词: Leishmania (L.) infantum chagasi;    visceral leishmaniasis;    isobenzofuranones;    phthalides;    in vitro leishmanicidal activity;   

DOI  :  10.3390/molecules201219857

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.