de Araújo Morgana V, David Cibelle Cabral, Neto José Clementino, de Oliveira Luiz A P L, da Silva Karoline Cristina Jatobá, Dos Santos Jefferson Miguel, da Silva João Kayke S, de A Brandão Victoria B C, Silva Tania M S, Camara Celso A, Alexandre-Moreira Magna S
Laboratory of Pharmacology and Immunity, Institute of Biological Sciences and Health, Federal University of Alagoas, 57020-720, Maceió, AL, Brazil.
Laboratory of Bioactive Compounds Synthesis, Molecular Sciences Department, Federal Rural University of Pernambuco, 52171-900, Recife, PE, Brazil.
Exp Parasitol. 2017 May;176:46-51. doi: 10.1016/j.exppara.2017.02.004. Epub 2017 Feb 4.
Parasites of the Leishmania genus are the causative agents of leishmaniasis in humans, a disease that affects more than 12 million people worldwide. In this study was evaluated in vitro leishmanicidal activity of 2-N,N'-dialkylamino-1,4-naphthoquinone derivatives, covering a series of fourteen 2-N-morpholino-, 2-N-thiomorpholino, 2-N-piperidino, 2-N-(N-methyl)-piperazino naphthoquinones (1a-n) derived from nor-lapachol and lawsone, belong to some other di-alkyaminoderivatives. At the cytotoxicity assay on peritoneal macrophages, the compounds possessing larger alkyl groups and N-methyl-piperazino moiety (1d, 1h, 1i and 1k), showed toxic effects similar to the standard drug used pentamidine. However, the other compounds of the series showed no deleterious effect on the host cell. Meanwhile, these cytotoxic derivatives (1d, 1h and 1i) had pronounced leishmanicidal activity against L. amazonensis promastigotes, and treatments with six other compounds (1d, 1e, 1f, 1h, 1k and 1n) had significant effect leishmanicidal against L. chagasi promastigotes. In the assay against L. chagasi amastigotes, eight compounds (1a, 1b, 1c, 1d, 1h, 1i, 1k and 1m) showed significant activity. Moreover, the compounds (1a, 1b, 1c, and 1m) showed effect against amastigotes of L. chagasi and not being toxic to the host cell. These data show the derivatives as promising substances for research leishmanicidal activity.
利什曼原虫属的寄生虫是人类利什曼病的病原体，这种疾病在全球影响着超过1200万人。在本研究中，评估了2-N,N'-二烷基氨基-1,4-萘醌衍生物的体外杀利什曼原虫活性，该系列包括十四种由去甲拉帕醇和拉索酸衍生的2-N-吗啉代、2-N-硫代吗啉代、2-N-哌啶基、2-N-(N-甲基)-哌嗪基萘醌(1a-n)，以及一些其他二烷基氨基衍生物。在对腹腔巨噬细胞的细胞毒性试验中，具有较大烷基和N-甲基哌嗪基部分的化合物(1d、1h、1i和1k)表现出与标准药物喷他脒相似的毒性作用。然而，该系列的其他化合物对宿主细胞没有有害影响。同时，这些细胞毒性衍生物(1d、1h和1i)对亚马逊利什曼原虫前鞭毛体具有显著的杀利什曼原虫活性，另外六种化合物(1d、1e、1f、1h、1k和1n)对恰加斯利什曼原虫前鞭毛体具有显著的杀利什曼原虫作用。在针对恰加斯利什曼原虫无鞭毛体的试验中，八种化合物(1a、1b、1c、1d、1h、1i、1k和1m)表现出显著活性。此外，化合物(1a、1b、1c和1m)对恰加斯利什曼原虫无鞭毛体有作用且对宿主细胞无毒。这些数据表明这些衍生物是有前景的研究杀利什曼原虫活性的物质。
