Portal de Periódicos da CAPES

Synthesis, characterization and antimalarial activity of quinoline–pyrimidine hybrids

2012; Elsevier BV; Volume: 21; Issue: 1 Linguagem: Inglês

10.1016/j.bmc.2012.10.019

1464-3391

Stefan I. Pretorius, Wilma Breytenbach, Carmen De Kock, Peter J. Smith, David D. N’Da,

Phenothiazines and Benzothiazines Synthesis and Activities

The aim of this study was to synthesize a series of quinoline-pyrimidine hybrids and to evaluate their in vitro antimalarial activity as well as cytotoxicity. The hybrids were brought about in a two-step nucleophilic substitution process involving quinoline and pyrimidine moieties. They were screened alongside chloroquine (CQ), pyrimethamine (PM) and fixed combinations thereof against the D10 and Dd2 strains of Plasmodium falciparum. The cytotoxicity was determined against the mammalian Chinese Hamster Ovarian cell line. The compounds were all active against both strains. However, hybrid (21) featuring piperazine linker stood as the most active of all. It was found as potent as CQ and PM against the D10 strain, and possessed a moderately superior potency over CQ against the Dd2 strain (IC(50): 0.157 vs 0.417 μM, ∼threefold), and also displayed activity comparable to that of the equimolar fixed combination of CQ and PM against both strains.