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Table 2 A list of efficient anti-malarial aaRS inhibitors

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 IC50 ~ 90 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 50 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 9 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, 4749]
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]