N-1-cyclohexyl-N-2-[(1-methyl-2-oxo-2,3-dihydro-1H-indol-5-yl)sulfonyl]glycinamide

Chemical Formula: C17H23N3O4S

Molecular Weight: 365.4546

OTAVAchemicals Catalogue Number: 1458183

CAS Registry Number: 1216772-20-1

Purity: 95% (HPLC)

Ref.: A. Contet et al. Plasmodium falciparum CTP: phosphocholine cytidylyltransferase possesses two functional catalytic domains and is inhibited by a CDP-choline analog selected from a virtual screening. FEBS Letters (2015), 589 (9), 992-1000

Abstract: Phosphatidylcholine is the major lipid component of the malaria parasite membranes and is required for parasite multiplication in human erythrocytes. Plasmodium falciparum CTP:phosphocholine cytidylyl transferase (PfCCT) is the rate-limiting enzyme of the phosphatidylcholine biosynthesis pathway and thus considered as a potential antimalarial target. In contrast to its mammalian orthologs, PfCCT contains a duplicated catalytic domain. Here, we show that both domains are catalytically active with similar kinetic parameters. A virtual screening strategy allowed the identification of a drug-size molecule competitively inhibiting the enzyme. This compound also prevented phosphatidylcholine biosynthesis in parasites and exerted an antimalarial effect. This study constitutes the first step towards a rationalized design of future new antimalarial agents targeting PfCCT.

DOI: 10.1016/j.febslet.2015.03.003