4-Aminoquinoline Derivatives as Potential Antileishmanial Agents

被引：43

作者：

Antinarelli, Luciana M. R. ^{[1
]}

Dias, Rafael M. P. ^{[2
]}

Souza, Isabela O. ^{[2
]}

Lima, Wallace P. ^{[3
]}

Gameiro, Jacy ^{[1
]}

da Silva, Adilson D. ^{[2
]}

Coimbra, Elaine S. ^{[1
]}

机构：

[1] Univ Fed Juiz de Fora, Dept Parasitol Microbiol & Imunol, Inst Ciencias Biol, BR-36036900 Juiz De Fora, Brazil

[2] Univ Fed Juiz de Fora, Inst Ciencias Exatas, Dept Quim, BR-36036900 Juiz De Fora, Brazil

[3] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Lab Imunofarmacol, BR-21941902 Rio De Janeiro, Brazil

来源：

CHEMICAL BIOLOGY & DRUG DESIGN | 2015年 / 86卷 / 04期

关键词：

aminoquinoline; Leishmania; Leishmania amazonensis; mitochondrial membrane potential; reactive oxygen species; VISCERAL LEISHMANIASIS; CUTANEOUS LEISHMANIASIS; OXIDATIVE STRESS; ORAL MILTEFOSINE; AMAZONENSIS; 8-AMINOQUINOLINE; QUINOLINES; PROMASTIGOTES; SITAMAQUINE; TAFENOQUINE;

D O I：

10.1111/cbdd.12540

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The leishmanicidal activity of a series of 4-aminoquinoline (AMQ) derivatives was assayed against Leishmania amazonensis. This activity against the intracellular parasite was found stronger than for L.amazonensis promastigotes. Neither compound was cytotoxic against macrophages. The compound AMQ-j, which exhibited a strong activity against promastigotes and amastigotes of L.amazonensis (IC50 values of 5.9 and 2.4g/mL, respectively) and similar leishmanicidal activity to reference drugs, was chosen for studies regarding its possible mechanism of action toward parasite death. The results showed that the compound AMQ-j induced depolarization of the mitochondrial membrane potential in promastigotes and in L.amazonensis-infected macrophages, but not in uninfected macrophages. Furthermore, the depolarization of the mitochondrial membrane potential was dose dependent in infected macrophages. We have established that promastigotes and L.amazonensis-infected macrophages treated with AMQ-j were submitted to oxidative stress. This is in line with the increase in the level of reactive oxygen species (ROS). Leishmania amazonensis-infected macrophages treated with AMQ-j did not show a significant increase in the production of nitric oxide. Our results indicate the effective and selective action of AMQ-j against L.amazonensis, and its mechanism of action appears to be mediated by mitochondrial dysfunction associated with ROS production.

引用

页码：704 / 714

页数：11

共 35 条

[1]

Antinarelli L. M., 2012, ORG MED CHEM LETT, V2, P1

[2] ISOLATION OF LEISHMANIA-MEXICANA-AMAZONENSIS FROM THE BONE-MARROW IN A CASE OF AMERICAN VISCERAL LEISHMANIASIS [J].