Anti-leishmanial evaluation of C2-aryl quinolines: Mechanistic insight on bioenergetics and sterol biosynthetic pathway of Leishmania braziliensis

被引：23

作者：

Bompart, Daznia ^{[1
]}

Nunez-Duran, Jorge ^{[1
]}

Rodriguez, Daniel ^{[2
]}

Kouznetsov, Vladimir V. ^{[4
]}

Melendez Gomez, Carlos M. ^{[4
]}

Sojo, Felipe ^{[3
]}

Arvelo, Francisco ^{[3
,5
]}

Visbal, Gonzalo ^{[6
]}

Alvarez, Alvaro ^{[6
]}

Serrano-Martin, Xenon ^{[1
]}

Garcia-Marchan, Yael ^{[1
]}

机构：

[1] Inst Estudios Avanzados IDEA, Lab Senalizac Celular & Bioquim Parasitos, Area Salud, Caracas, Venezuela

[2] Inst Estudios Avanzados IDEA, Lab Pesquisa Select, Area Salud, Caracas, Venezuela

[3] Inst Estudios Avanzados IDEA, Area Salud, Caracas, Venezuela

[4] Univ Ind Santander, Lab Quim Organ & Biomol, Bucaramanga, Colombia

[5] Cent Univ Venezuela, Lab Cultivo Tejidos & Biol Tumores, IBE, Caracas, Venezuela

[6] Inst Venezolano Invest Cient, Ctr Quim, Lab Sintesis Organ & Compuestos Nat, Caracas, Venezuela

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2013年 / 21卷 / 14期

关键词：

Chemotherapy; L; braziliensis; Parasite bioenergetics; Sterol biosynthetic pathway; C2-aryl substituted quinolines; DIELS-ALDER REACTIONS; IN-VITRO; 2-SUBSTITUTED QUINOLINE; SUBSTITUTED QUINOLINES; SITAMAQUINE; DONOVANI; AGENTS; 8-AMINOQUINOLINE; ACIDOCALCISOMES; CHEMOTHERAPY;

D O I：

10.1016/j.bmc.2013.04.063

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：

A series of diverse simple C2-aryl quinolines was synthesized de novo via a straightforward synthesis based on the acid-catalyzed multicomponent imino Diels-Alder reactions. Seven selected quinolines were evaluated at different stages of Leishmania braziliensis parasite. Among them, the 6-ethyl-2-phenylquinoline 5f was able to inhibit the growth of promastigotes of this parasite without affecting the mammalian cells viability and decreasing the number of intracellular L. braziliensis amastigotes on BMDM macrophages. The mechanism of action studied for the selected compound consisted in: (1) alteration of parasite bioenergetics, by disrupting mitochondrial electrochemical potential and alkalinization of acidocalcisomes, and (2) inhibition of ergosterol biosynthetic pathway in promastigote forms. These results validate the efficiency of quinoline molecules as leishmanicide compounds. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：4426 / 4431

页数：6

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