Compounds that target isoprenoid biosynthesis in plasmodium falciparum could be a welcome addition to malaria chemotherapy, since the methylerythritol phosphate (MEP) pathway used by the parasite is not present in humans. MMV008138 targets the apicoplast of P. falciparum and that its target in the MEP pathway differs from that of Fosmidomycin. The active stereoisomer of MMV008138 was (1R,3S)-configured which was found to be crucial for inhibition of the parasite growth as a MEP pathway-targeting antimalarial agent. Recently some researchers have claimed that they identified the molecular target of MMV008138 as IspD, the third enzyme of the MEP pathway.
References
1) Yao, Zhong-Ke, Krai, Priscilla M. et al. “Determination of the active stereoisomer of the MEP pathway-targeting antimalarial agent MMV008138, and initial structure-activity studies.” Bioorganic & Medicinal Chemistry Letter, 2015, 25, 1515-1519
2) Wu, W., Herrera, Z, Ebert, D. Baska, K.; Cho, S.H.; Derisi, J. I.; Yeh, E. “A Chemical Rescue Screen Identifies a Plasmodium falciparum Apicoplast Inhibitor Targeting MEP Isoprenoid Precursor Biosynthesis” Antimicrob. Agents Chemother. 2015, 59, 356-364.
