quinine and artenimol

The aim of this study was to provide the first comprehensive spatiotemporal picture of Plasmodium falciparum resistance in various geographic areas in Madagascar. Additional data about the antimalarial resistance in the neighboring islands of the Comoros archipelago were also collected. We assessed the prevalence of pfcrt, pfmdr-1, pfdhfr, and pfdhps mutations and the pfmdr-1 gene copy number in 1,596 P. falciparum isolates collected in 26 health centers (20 in Madagascar and 6 in the Comoros Islands) from 2006 to 2008. The in vitro responses to a panel of drugs by 373 of the parasite isolates were determined. The results showed (i) unusual profiles of chloroquine susceptibility in Madagascar, (ii) a rapid rise in the frequency of parasites with both the pfdhfr and the pfdhps mutations, (iii) the alarming emergence of the single pfdhfr 164L genotype, and (iv) the progressive loss of the most susceptible isolates to artemisinin derivatives. In the context of the implementation of the new national policy for the fight against malaria, continued surveillance for the detection of P. falciparum resistance in the future is required.

Topics: Animals; Antimalarials; Artemisinins; Chloroquine; Dihydropteroate Synthase; Drug Combinations; Drug Resistance; Haplotypes; Madagascar; Multidrug Resistance-Associated Proteins; Parasitic Sensitivity Tests; Plasmodium falciparum; Pyrimethamine; Sulfadoxine; Tetrahydrofolate Dehydrogenase

A new series of hydrolytically stable and water-soluble dihydroartemisinin derivatives with optically active side chains was prepared as potential antimalarial agents. This was an effort to prepare compounds with activity superior to that of artelinic acid and to examine the impact of the stereospecificity of the introduced alkyl side chain on biological properties. The ester derivatives (6a-d) possess superior in vitro activity to artemisinin, artemether, and arteether against two strains of Plasmodium falciparum (D-6 and W-2); however, conversion of the esters to their corresponding acids drastically reduces their antimalarial activity. None of the new acids possess in vitro antimalarial activity superior to that of artelinic acid. Although there appears to be limited stereospecificity for antimalarial activity among the acids (7a-d) tested, significant differences in antimalarial activity was seen among the esters.

Topics: Animals; Artemisinins; Chemical Phenomena; Chemistry; Malaria; Mice; Molecular Structure; Plasmodium falciparum; Sesquiterpenes; Solubility; Stereoisomerism; Structure-Activity Relationship; Water