Name: Zhai, Lin Home Country: China Research Country: China Project Period: 1995-1998   Title Mechanism of Action of Oxygenated Chalcones on Human Pathogenic Protozoan Leishmania Abstract The goal of this study was to investigate the mechanism of action of the antileishmanial oxygenated chalcones. The data demonstrated that the oxygenated chalcones exhibit potent antileishmanial activity. Electron microscopic studies showed that they destroyed the mitochondria of the Leishmania promastigote, while the other organelles of the parasite appeared normal. They also destroyed the mitochondria of the Leishmania amastigote, while the organelles of the host macrophage remained normal. Experiments were carried out to examine the effect of oxygenated chalcones on the function of the parasite mitochondria. The dada showed that oxygenated chalcones inhibited the respiration of the parasite, as shown by the alteration of 02 consumption and C02 production, and the activity of the parasite mitochondrial dehydrogenase. The inhibition of the mitochondrial function of the parasite correlated well with the changes in the ultrastructure of the mitochondria. Further investigation on the activity of me enzymes in the parasite respiratory chain showed that oxygenated chalcones specifically target the FRD of the parasite. Conclusion The data presented in this thesis demonstrate that oxygenated chalcones exhibited potent antileishmanial activity. The antileishmanial activity was shown to be associated with alteration of the ultrastructure and the function of the parasite mitochondria. Besides, the alteration of the respiration and mitochondrial dehydrogenase of the parasite correlated well with the changes in the ultrastructure of the mitochondria. Further investigation on the activity of some enzymes in the parasite respiratory chain showed that oxygenated chalcones specifically target the FRD of the parasite. In conclusion, the main findings presented in this thesis is that the antileishmanial oxygenated chalcones alter the ultrastructure and the function of the mitochondria of the parasite, and the FRD in the parasite respiratory chain might be their specific target. Furthermore, FRD could be a suitable target for antileishmanial drugs. Further studies It is necessary to further investigate whether oxygenated chalcones also have other targets in the parasite than the FRD and the mitochondria. Since little research has been done on the energy metabolism of Leishmania parasite, further study on this aspect is warranted, which may help to design new antileismanial drugs    Involved research institution(s) Centre for Medical Parasitology, Department of Clinical Microbiology, University of Copenhagen The State Serum Institute, Copenhagen Supervisor(s) Arsalan Kharazmi, State University Hospital, Copenhagen Thor Theander, Centre for Medical Parasitology Correspondence