Investigations of the Reasons for the Susceptibility of Schizogony as a Target for Chemotherapeutic Attack in Malaria Parasites.
Final technical rept.,
KENT UNIV CANTERBURY (ENGLAND) BIOLOGICAL LAB
Pagination or Media Count:
There is good evidence that the activity of the widely used antimalaria agent, pyrimethamine, against the intraerythrocytic stages of malaria parasites is directed towards one particular part of the cell cycle - schizogony. The final objective of these investigations is to understand in molecular terms why and how the process of schizogony is susceptible to such chemotherapeutic attack. This report is concerned in part with the development of the methodology necessary for the subsequent biochemical investigation of this activity. Thus it describes an in vitro system in which Plasmodium chabaudi will grow. It also outlines the problems that have been encountered in attempts to label parasites in vitro with radiotracers, a vital preliminary to the main biochemical study. A complementary investigation of the effects of pyrimethamine on the ultrastructure of P. chabaudi is reported. It is clear from this study that there is more to the action of the drug than inhibition of DNA synthesis. The report concludes with an account of the mechanism of dihydro-orotate dehydrogenase, one of the enzymes of the de novo biosynthetic pathway for pyrimidines.