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Lipid Targets Of The Antimalarial Trioxanes In Plasmodium Falciparum, Carmony Leah Hartwig
Lipid Targets Of The Antimalarial Trioxanes In Plasmodium Falciparum, Carmony Leah Hartwig
Biological Sciences Theses & Dissertations
Malaria is among the most debilitating diseases of man. The protozoan parasite, Plasmodium falciparum, causes over a million annual fatalities. The antimalarial trioxanes, exemplified by artemisinin, are among the few pharmaceuticals for which clinical resistance has not become widespread. Artemisinin is a naturally occurring sesquiterpene lactone, containing a unique endoperoxide pharmacophore. Despite extensive study, the precise antimalarial mechanism of action of trioxanes remains elusive. Heme iron-mediated cleavage of the endoperoxide within the parasite digestive vacuole is hypothesized to generate cytotoxic metabolites capable of alkylating heme and damaging cellular macromolecules. The hypothesis of this research is that the endoperoxide pharmacophore …
The Plasmodium Falciparum Chloroquine Resistance Transporter, Pfcrt, Mediates The Activity Of Chloroquine-Resistance Reversal Agents In The Malaria Parasite, Kristin Lane
Biological Sciences Theses & Dissertations
Chloroquine (CQ) resistant Plasmodium falciparum is a serious problem affecting 3.2 billion people in over 100 countries today. Most endemic malarious countries are among the poorest in the world and lack the resources to replace the inexpensive and highly effective CQ. CQ resistance (CQR) reversal agents are a potentially inexpensive solution to restoring CQ efficacy. CQR reversal agents are drugs that have little to no antimalarial activity alone, but in combination with CQ, they increase dmg accumulation in the parasite and enhance the sensitivity to CQ in CQR parasites. PfCRT is a putative transporter located on the parasite digestive vacuole …