From: Recent advances in the biology and drug targeting of malaria parasite aminoacyl-tRNA synthetases
Inhibitor | Target plasmoDB geneID | Comment |
---|---|---|
Mupirocin | IleRS PF3D7_1225100 | This is a clinical inhibitor of bacterial infection by S. aeurus. Likely targets active site of apicoplast IleRS with IC50Â ~Â 90Â nM [21] |
4-Thiaisoleucine | IleRS PF3D7_1332900 | Structural analogue of isoleucine targets the cytoplasmic IleRS [21] |
TCMDC-131575 | IleRS PF3D7_1332900 | Molecule identified in GlaxoSmithKline’s library screening. IleRS is the hypothesized target [45] |
Cladosporin | LysRS PF3D7_1350100 | A selective malaria inhibitor with IC50 value near 50Â nM. Kills both liver and blood stage parasites. Drug bound crystal structure is available [40, 41] |
Lysyl-adenylate analogues | LysRS PF3D7_1416800 | Nearly 50 analogues with μM inihibition reported [46] |
Halofuginone | ProRS PF3D7_1213800 | Inhibit both liver and blood stages. Bind to parasite enzyme with Kd value of 9Â nM. Halofuginone bound crystal structure is available [43, 52, 55] |
Borrelidin and analogues | ThrRS PF3D7_1126000 | Kills P. falciparum at IC50 near 1 nM. ThrRS inhibition confirmed in enzyme assays [40]. Analogs with reduced cytotoxicity to human were reported [42, 47–49] |
A5, A3 | AlaRS PF3D7_1367700 | Several P. falciparum inhibitors identified using in silico screening and docking against active site. A5 was top inhibitor with IC50 value near 4 μM [18] |
TCMDC-141232 | TyrRS PF3D7_1117500 | Molecule identified in GlaxoSmithKline’s library screening. Apicoplast copy of TyrRS is the hypothesized target [45] |
REP3123 REP8839 C1–C8 | MetRS PF3D7_1034900 | Known bacterial MetRS inhibitors REP3123 and REP8839 inhibit P. falciparum and block translation with IC50 values near 150 nM. C1–C8 identified from in silico screening and inhibit parasite growth with IC50 values below 500 nM [24] |
TCMDC-140014 TCMDC-139627 TCMDC-139450 | MetRS PF3D7_1034900 | Molecules identified in GlaxoSmithKline’s library screening. MetRS is the hypothesized target [45] |
Sulfomyl adenosine analogues | SerRS PF3D7_071770 GluRS PF3D7_1349200 GlnRS PF3D7_1331700 AsnRS PF3D7_0211800 TyrRS PF3D7_0807900 | Mechanism based inhibitors that mimic the intermediate aminoacyl-AMP were tested and shown to kill malaria parasite in nM values [42] |
AN2729 | LeuRS PF3D7_0828200 | Member of benzoxaborols family which show anti-malarial activity [42] |
TCMDC-140398 TCMDC-140498 TCMDC-140522 TCMDC-140563 TCMDC-140564 TCMDC-140734 TCMDC-141485 | PheRS PF3D7_1104000 | Molecule identified in GlaxoSmithKline’s library screening. Cytoplasmic copy of PheRS is the hypothesized target [45] |