New pentasubstituted pyrrole hybrid atorvastatin-quinoline derivatives with antiplasmodial activity

被引：43

作者：

Carvalho, Rita C. C. ^{[1
,2
]}

Martins, Wagner A. ^{[1
]}

Silva, Tayara P. ^{[3
]}

Kaiser, Carlos R. ^{[2
]}

Bastos, Monica M. ^{[1
]}

Pinheiro, Luiz C. S. ^{[1
]}

Krettli, Antoniana U. ^{[3
]}

Boechat, Nubia ^{[1
]}

机构：

[1] Farmanguinhos FIOCRUZ, Dept Sintese Farmacos, Inst Tecnol Farmacos, Rua Sizenando Nabuco 100, BR-21041250 Rio De Janeiro, RJ, Brazil

[2] Univ Fed Rio de Janeiro, PGQu Inst Quim, Programa Pos Grad Quim, Rio De Janeiro, RJ, Brazil

[3] CPqRR FIOCRUZ, Lab Malaria, Ctr Pesquisas Rene Rachou, BR-30190002 Belo Horizonte, MG, Brazil

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2016年 / 26卷 / 08期

关键词：

Malaria; Atorvastatin; Pentasubstituted pyrrole; Chloroquine; Primaquine; CEREBRAL MALARIA; TRISUBSTITUTED PYRROLE; ANTIMALARIAL-DRUGS; IN-VITRO; PLASMODIUM; STATINS; MEFLOQUINE;

D O I：

10.1016/j.bmcl.2016.03.027

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Cerebral malaria is caused by Plasmodium falciparum. Atorvastatin (AVA) is a pentasubstituted pyrrole, which has been tested as an adjuvant in the treatment of cerebral malaria. Herein, a new class of hybrids of AVA and aminoquinolines (primaquine and chloroquine derivatives) has been synthesized. The quinolinic moiety was connected to the pentasubstituted pyrrole from AVA by a linker group (CH2)(n) = 2-4 units. The activity of the compounds increased with the size of the carbons chain. Compound with n = 4 and 7-chloroquinolinyl has displayed better activity (IC50 = 0.40 mu M) than chloroquine. The primaquine derivative showed IC50 = 1.41 mu M, being less toxic and more active than primaquine. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：1881 / 1884

页数：4

共 44 条

[1]

[Anonymous], 2014, World Malaria Report

[2] Pyrrole: a resourceful small molecule in key medicinal hetero-aromatics [J].