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

• Published in: Molecules (Basel, Switzerland) Vol. 20; no. 12; pp. 22435 - 22444
• Main Authors: Pereira, Wagner Luiz, de Souza Vasconcellos, Raphael, Mariotini-Moura, Christiane, Saar Gomes, Rodrigo, Firmino, Rafaela de Cássia, da Silva, Adalberto Manoel, Silva Júnior, Abelardo, Bressan, Gustavo Costa, Almeida, Márcia Rogéria, Crocco Afonso, Luís Carlos, Teixeira, Róbson Ricardo, Lopes Rangel Fietto, Juliana
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 14-12-2015; MDPI
• Subjects: Amphotericin B; Animals; Antiprotozoal Agents - pharmacology; Benzofurans - pharmacology; Cell Survival; Developing countries; Drug Evaluation, Preclinical; in vitro leishmanicidal activity; isobenzofuranones; LDCs; Leishmania; Leishmania (L.) infantum chagasi; Leishmania infantum - drug effects; Leishmaniasis - drug therapy; Macrophages; Macrophages - drug effects; Macrophages - parasitology; Medical treatment; Mice; Parasites; Parasitic diseases; phthalides; Promastigotes; Protozoa; RAW 264.7 Cells; Vector-borne diseases; Viability; Visceral leishmaniasis; phthalides; in vitro leishmanicidal activity; visceral leishmaniasis; Leishmania (L.) infantum chagasi; isobenzofuranones
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules201219857

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.