In vitro inhibition of Plasmodium falciparum by pyrazofurin, an inhibitor of pyrimidine biosynthesis de novo |
| |
| Authors: | H V Scott A M Gero W J O'Sullivan |
| |
| Affiliation: | 1. Army Malaria Research Unit, Milpo, Ingleburn, N.S.W. 2174, Australia;2. School of Biochemistry, University of New South Wales, P.O. Box 1, Kensington, N.S.W. 2033, Australia;1. Division of Chemistry, Department of Sciences & Humanities, Vignan’s Foundation for Science Technology and Research (Deemed to be University), Vadlamudi, Andhra Pradesh 522213, India;2. Department of Surgery, Boston University School of Medicine, Boston 02118, MA, USA;3. Department of Chemistry, St. Berchmans College (Autonomous), Changanassery, Kerala, India;4. Neuland Laboratories Ltd., Hyderabad 500034, Telangana, India;1. Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N.P. Marg, Matunga, Mumbai 400019, Maharashtra, India;2. Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400005, Maharashtra, India;1. Mycotic and Parasitic Agents and Mycobacteria (FG16), Robert Koch Institute, Berlin, Germany;2. Metabolism of Microbial Pathogens (NG2), Robert Koch Institute, Berlin, Germany;3. Department of Biochemistry and Pharmacology, Bio21 Institute of Molecular Science and Biotechnology, University of Melbourne, Melbourne, Australia;4. Advanced Light and Electron Microscopy (ZBS 4), Robert Koch Institute, Berlin, Germany |
| |
| Abstract: | The effect of pyrazofurin, an inhibitor of UMP synthesis, on Plasmodium falciparum growth in vitro has been studied. ID50 values (concentration of compound causing 50% inhibition of [3H]hypoxanthine incorporation) for the FCQ-27, FCI-1 and K-1 (chloroquine-resistant) isolates were 10 +/- 8.7, 6.4 +/- 5.3 and 6.3 +/- 0.5 microM, respectively. Comparative ID50 values for chloroquine were 13.5 +/- 4.2, 22.8 +/- 7.6 and 343 +/- 114 microM, respectively. Over the 48-h intraerythrocytic cycle of tightly synchronized parasites, pyrazofurin both reduced the parasitemia and retarded the maturation of trophozoites and schizonts. Addition of uracil or uridine to the in vitro culture did not decrease the anti-parasitic activity of pyrazofurin. Chloroquine reduced the parasitemia, but did not retard development of the remaining viable parasites. Pyrazofurin (20 microM) caused a 50% inhibition of parasite orotate phosphoribosyltransferase (E.C. 2.4.2.10) and, in the presence of adenosine kinase and ATP, a 73% inhibition of orotidine-5'-phosphate decarboxylase (E.C. 4.1.1.23). |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
