Several drug development strategies, including optimization of new antimalarial drug combinations, have been used to counter malaria drug resistance. We evaluated the malaria Sybr green I-based fluorescence (MSF) assay for its use in in vitro drug combination sensitivity assays. Drug combinations of previously published synergistic (atovaquone and proguanil), indifferent (chloroquine and azithromycin), and antagonistic (chloroquine and atovaquone) antimalarial drug interactions were tested against Plasmodium falciparum strains D6 and W2 using the MSF assay.
BACKGROUND: Artemisinin-based combination therapies are the recommended first-line treatments of falciparum malaria in all countries with endemic disease. There are recent concerns that the efficacy of such therapies has declined on the Thai-Cambodian border, historically a site of emerging antimalarial-drug resistance.
Emergence of artemisinin resistance in Cambodia highlights the importance of characterizing resistance to this class of drugs. Previously, intermediate levels of resistance in Plasmodium falciparum were generated in vitro for artelinic acid (AL) and artemisinin (QHS). Here we expanded on earlier selection efforts to produce levels of clinically relevant concentrations, and the resulting lines were characterized genotypically and phenotypically. Recrudescence assays determined the ability of resistant and parent lines to recover following exposure to clinically relevant levels of drugs.
BACKGROUND: The aim of the present work was to assess i) ex vivo activity of pyronaridine (PND) and piperaquine (PPQ), as new components of artemisinin-based combination therapy (ACT), to define susceptibility baseline, ii) their activities compared to other partner drugs, namely monodesethylamodiaquine (MDAQ), lumefantrine (LMF), mefloquine (MQ), artesunate (AS) and dihydroartemisinin (DHA) against 181 Plasmodium falciparum isolates from African countries, India and Thailand, and iii) in vitro cross-resistance with other quinoline drugs, chloroquine (CQ) or quinine (QN).
BACKGROUND: Semi-synthetic artemisinin derivatives are powerful peroxidic drugs in artemisinin-based combination therapy (ACT) recommended as first-line treatment of Plasmodium falciparum malaria in disease-endemic countries. Studies by Eckstein-Ludwig and co-workers showed both thapsigargin and artemisinin specifically inhibit the sarcoplasmic reticulum Ca²?-ATPase of Plasmodium falciparum (PfATP6). In the present study the type of interaction between thapsigargin and artemisinin derivatives as well as the ozonide OZ277 (RBx11160 or arterolane) was evaluated in parasite cultures.
Two drugs composed of several different plant extracts are in use in Ayurvedic medicine for the treatment of asthma and arthritis, respectively. There is increasing evidence that reactive oxygen species (ROS) arising from several enzymatic reactions are mediators of inflammatory events such as the above mentioned. Plant extracts have the potential for scavenging such reactive oxygen species, dependent on the individual test system.