Cupello Mauricio Peixoto, Saraiva Francis Monique, Ippolito Pedro, Fernandes Andréia da Silva, Menna-Barreto Rubem Figueiredo Sadoko, Costa Debora de Sousa Dos Santos, Paula Jessica Isis Oliveira, Costa Paulo Roberto Ribeiro, Nogueira Natália Pereira, Felzenswalb Israel, Dias Ayres Guimarães, Paes Marcia Cristina
Laboratório de Interação Tripanossomatídeos e Vetores, Departamento de Bioquímica, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil; Unidade de Desenvolvimento Tecnológico (UDT) de Triagem de Compostos Químicos para Doenças Negligenciadas com Ênfase Farmacológica contra a Doença de Chagas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Laboratório de Interação Tripanossomatídeos e Vetores, Departamento de Bioquímica, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Biomed Res Int. 2017;2017:2483652. doi: 10.1155/2017/2483652. Epub 2017 Feb 15.
The therapeutic options for Chagas disease are limited and its treatment presents a number of drawbacks including toxicity, drug resistance, and insufficient effectiveness against the chronic stage of the disease. Therefore, new therapeutical options are mandatory. In the present work, we evaluated the effect of a phenyl--butylnitrone (PBN) derivate, LQB 123, against forms. LQB 123 presented a trypanocidal effect against bloodstream trypomastigotes (IC = 259.4 ± 6.1 M) and intracellular amastigotes infecting peritoneal macrophages (IC = 188.2 ± 47.5 M), with no harmful effects upon the mammalian cells (CC values greater than 4 mM), resulting in a high selectivity index (CC/IC > 20). Additionally, metacyclic trypomastigotes submitted to LQB 123 presented an IC of about 191.8 ± 10.5 M and epimastigotes forms incubated with different concentrations of LQB 123 presented an inhibition of parasite growth with an IC of 255.1 ± 3.6 M. Finally, we investigated the mutagenic potential of the nitrone by the /microsome assay and observed no induction of mutagenicity even in concentrations as high as 33000 M. Taken together, these results present a nonmutagenic compound, with trypanocidal activity against all relevant forms of , offering new insights into CD treatment suggesting additional in vivo tests.
恰加斯病的治疗选择有限，其治疗存在诸多弊端，包括毒性、耐药性以及对疾病慢性阶段疗效不足等问题。因此，新的治疗选择势在必行。在本研究中，我们评估了一种苯基 - 丁基硝酮（PBN）衍生物LQB 123对不同形态的效果。LQB 123对血流型锥鞭毛体（IC = 259.4 ± 6.1 μM）以及感染腹腔巨噬细胞的细胞内无鞭毛体（IC = 188.2 ± 47.5 μM）具有杀锥虫作用，对哺乳动物细胞无有害影响（CC值大于4 mM），从而产生了较高的选择性指数（CC/IC > 20）。此外，接受LQB 123处理的循环后期锥鞭毛体的IC约为191.8 ± 10.5 μM，用不同浓度LQB 123孵育的前鞭毛体形态呈现出对寄生虫生长的抑制作用，IC为255.1 ± 3.6 μM。最后，我们通过/微粒体试验研究了该硝酮的诱变潜力，即使在高达33000 μM的浓度下也未观察到诱变作用。综上所述，这些结果表明该化合物无诱变作用，对所有相关形态的具有杀锥虫活性，为恰加斯病的治疗提供了新的见解，提示需进一步进行体内试验。
