1228 MFQ MTX nM PG PQ PRB PRQ PRN THF TMX uM WR99210 mefloquine methotrexate nanomolar proguanil piperaquine probenecid primaquine pyronaridine tetrahydrofolate trimetrexate micromolar Walter reed compound 99210 Fig. 1 Chemical structures of folic acid and of the antifolate drugs we analyzed Parasitol Res (2008) 102:1227–1234 Introduction Antifolates inhibit the synthesis and conversion of folate derivatives (FDs). Rapidly dividing cells such as cancer cells, bacteria, or malaria parasites rely heavily on the availability of folate to grow. Thus, blockade of synthesis of these factors greatly affects cell division. This feature has been exploited for the development of antifolate drugs. FDs is a generic term that consists of ten different forms of folate. The chemical structure of one of the FDs, folic acid (FA), is shown in Fig. 1, and the role of FDs has been discussed previously (Nzila et al. 2005a, b).