N-Cinnamoylation of Antimalarial Classics: Effects of Using Acyl Groups Other than Cinnamoyl toward Dual-Stage Antimalarials

被引：14

作者：

Gomes, Ana ^{[1
]}

Machado, Marta ^{[2
]}

Lobo, Lis ^{[3
]}

Nogueira, Fatima ^{[3
]}

Prudencio, Miguel ^{[2
]}

Teixeira, Catia ^{[1
]}

Gomes, Paula ^{[4
]}

机构：

[1] Univ Aveiro, Dept Quim, CICECO, P-3810193 Aveiro, Portugal

[2] Univ Lisbon, Inst Med Mol, Fac Med, P-1649028 Lisbon, Portugal

[3] Inst Higiene & Med Trop, Ctr Malaria & Outras Doencas Trop, P-1349008 Lisbon, Portugal

[4] Univ Porto, Dept Quim & Bioquim, UCIBIO REQUIMTE, Fac Ciencias, P-4169007 Oporto, Portugal

来源：

CHEMMEDCHEM | 2015年 / 10卷 / 08期

关键词：

antimalarial drugs; chloroquine; cinnamic acid; malaria; quinacrine; PLASMODIUM-FALCIPARUM; CHLOROQUINE; ANALOGS; PERMEABILITY; AGENTS;

D O I：

10.1002/cmdc.201500164

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In a follow-up study to our reports of N-cinnamoylated chloroquine and quinacrine analogues as promising dual-stage antimalarial leads with high in vitro potency against both blood-stage Plasmodium falciparum and liver-stage Plasmodium berghei, we decided to investigate the effect of replacing the cinnamoyl moiety with other acyl groups. Thus, a series of N-acylated analogues were synthesized, and their activities against blood- and liver-stage Plasmodiumspp. were assessed along with their in vitro cytotoxicities. Although the new N-acylated analogues were found to be somewhat less active and more cytotoxic than their N-cinnamoylated counterparts, they equally displayed nanomolar activities in vitro against blood-stage drug-sensitive and drug-resistant P.falciparum, and significant in vitro liver-stage activity against P.berghei. Therefore, it is demonstrated that simple N-acylated surrogates of classical antimalarial drugs are promising dual-stage antimalarial leads.

引用

页码：1344 / 1349

页数：6