Ivermectin-derived leishmanicidal compounds

被引：22

作者：

dos Santos, Anderson Rouge ^{[2
]}

Bandeira Falcao, Camila Alves ^{[3
]}

Muzitano, Michelle Frazao ^{[3
,4
]}

Kaiser, Carlos Roland ^{[2
]}

Rossi-Bergmann, Bartira ^{[3
]}

Ferezou, Jean-Pierre ^{[1
]}

机构：

[1] Ecole Polytech, DCSO, UMR 7652, CNRS, F-91128 Palaiseau, France

[2] Univ Fed Rio de Janeiro, Inst Quim, Ilha Fundao, CT, BR-21941909 Rio De Janeiro, Brazil

[3] Univ Fed Rio de Janeiro, Ilha Fundao, Inst Biofis Carlos Chagas Filho, CCS, BR-21941590 Rio De Janeiro, Brazil

[4] Univ Estadual Norte Fluminense, Ctr Biociencias & Biotecnol, BR-28013602 Campos Dos Goytacazes, RJ, Brazil

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2009年 / 17卷 / 02期

关键词：

Ivermectin; Avermectins; Seco-analogues; Ozonolysis; Leishmania; Leishmanicidal activity; Promastigotes; Amastigotes; CHEMOTHERAPY; MACROPHAGES;

D O I：

10.1016/j.bmc.2008.12.003

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：

In the present study a family of macrocyclic and acyclic analogues as well as seco-analogues of avermectins were prepared from commercial Ivermectin (IVM) and their antileishmanial activity assayed against axenic promastigote and intracellular amastigote forms of Leishmania amazonensis. Contrarily to the filaricidal activity, the leishmanicidal potentiality of avermectin analogues does not appear to depend on the integrity of the non-conjugated Delta(3,4)- hexahydrobenzofuran moiety. Conjugated Delta(2,3)- IVM or its corresponding conjugated secoester show higher anti-leishmania activity than the parent compound. Surprisingly, the diglycosylated northern sub-unit exhibits the same anti-amastigote potentiality as the southern hexahydrobenzofuran. As expected for compounds derived from the widely used Ivermectin antibiotic, little toxicity has been noticed for most of the novel analogues prepared. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：496 / 502

页数：7

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