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N‐Cinnamoylation of Antimalarial Classics: Effects of Using Acyl Groups Other than Cinnamoyl toward Dual‐Stage Antimalarials
Author(s) -
Gomes Ana,
Machado Marta,
Lobo Lis,
Nogueira Fátima,
Prudêncio Miguel,
Teixeira Cátia,
Gomes Paula
Publication year - 2015
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201500164
Subject(s) - plasmodium falciparum , plasmodium berghei , in vitro , moiety , pharmacology , chloroquine , chemistry , stereochemistry , malaria , biology , biochemistry , immunology
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 Plasmodium spp. 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.