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

• Main Authors: Wagner Luiz Pereira, Raphael de Souza Vasconcellos, Christiane Mariotini-Moura, Rodrigo Saar Gomes, Rafaela de Cássia Firmino, Adalberto Manoel da Silva, Abelardo Silva Júnior, Gustavo Costa Bressan, Márcia Rogéria Almeida, Luís Carlos Crocco Afonso, Róbson Ricardo Teixeira, Juliana Lopes Rangel Fietto
• Format: Article
• Language: English
• Published: MDPI AG 2015-12-01
• Series: Molecules
• Subjects: Leishmania (L.) infantum chagasi; visceral leishmaniasis; isobenzofuranones; phthalides; in vitro leishmanicidal activity
• Online Access: http://www.mdpi.com/1420-3049/20/12/19857

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.