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
Departamento de Química, Universidade Federal de Viçosa, Av. P.H. Rolfs, S/N, Viçosa, MG, 36.570-900, Brazil.
Departamento de Biologia Geral, Universidade Federal de Viçosa, Av. P.H. Rolfs, S/N, Viçosa, MG, 36.570-900, Brazil.
Molecules. 2015 Dec 14;20(12):22435-44. 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.
利什曼病是由利什曼原虫属的原生动物寄生虫引起的疾病。临床上，利什曼病从皮肤型到内脏型不等，全球估计年发病率分别为120万例和40万例。这些疾病的治疗依赖于用五价锑剂或两性霉素B进行多次非肠道注射。然而，这些药物对于发展中国家的常规使用来说，要么毒性太大，要么价格昂贵。这些事实需要更安全、更便宜且更有效的新型抗利什曼药物。在本研究中，我们描述了一系列异苯并呋喃-1(3H)-酮（苯酞）对婴儿利什曼原虫（利什曼原虫）恰加斯亚种活性评估的结果，该亚种是新世界内脏利什曼病的主要病原体。这些化合物在100、75、50、25和6.25 μM的浓度下进行了24、48和72小时的测试。在100 μM浓度下处理48小时后，化合物7和8分别将寄生虫活力降低至4%和6%。化合物7和8对前鞭毛体的抗利什曼活性在24小时后的半数最大效应浓度（LC50）分别为60.48和65.93 μM。此外，化合物7和8显著降低了巨噬细胞中的寄生虫感染。
Zotero 插件
