Dihydrofolate reductase and antifolate resistance in malaria.
The dihydrofolate reductase (DHFR, EC 1.5.1.3) domain of Plasmodium falciparum bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS) is an attractive target of two important antifolate antimalarials: pyrimethamine (Pyr) and cycloguanil (Cyc). Over recent years, knowledge of malarial DHFR and mechanism(s) of antifolate resistance have increased substantially. These observations have provided an important framework for better understanding the molecular basis of antifolate resistance in malaria. This article provides a brief review and update on molecular aspects relevant to antifolate resistance in malaria.
Sirawaraporn
W
W
Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand. scwsr@mucc.mahidol.ac.th