Table 1.
Inhibitors reported for different enzyme involved in the MEP pathway with their chemical properties.
| Gene/Protein | Enzyme | Inhibitor molecules | Inhibition mechanism | Organism with IC50 value | References | |
|---|---|---|---|---|---|---|
| DXS | 1-deoxy-D-xylose-5-phosphate (DXP) Synthase | *6-benzyl-3-(4-chlorophenyl)-5-methyl-2-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-7(4H)-one |  |
Competitive inhibition | M. tuberculosis (IC5010.6 μM) | Mao et al., 2008 |
| Ketoclomazone PubChem CID: 12811046 |  |
Non competitive inhibition | E. coli (IC50800 μg/mL) and H. influenzae (IC5012.5 μg/mL) | Matsue et al., 2010 | ||
| β-fluoropyruvate PubChem CID: 67946 |  |
Competitive inhibition | P. vivax (IC5035 ± 1.7 μM) P. falciparum (IC5043 ± 3.8 μM) | Battistini et al., 2016 | ||
| Methylacetylphosphonate PubChem CID: 23674726 |  |
Competitive inhibition | P. vivax (IC5080 μM) P. falciparum (IC5046 ± 3.8 μM) | |||
| IspC | DXP reductoisomerase | Fosmidomycin PubChem CID: 572 |  |
Competitive inhibition | P. falciparum (IC50350 ± 170 nM) | Jomaa et al., 1999; Lell et al., 2003; Umeda et al., 2011 |
| FR900098 PubChem CID: 162204 |  |
Competitive inhibition | P. falciparum (IC50170 ± 100 nM) | Jomaa et al., 1999 | ||
| *[1-(3,4-Difluorophenyl)-4-(hydroxylamino)-4-oxobutyl] phosphonic acid (Fosmidomycin reverse derivative) |  |
Competitive inhibition | P. falciparum (IC503 nM) | Behrendt et al., 2011 | ||
| *((3,4-Difluorophenyl)(2-(hydroxy(methyl)amino)-2-oxoethoxy)methyl) phosphonic acid |  |
Competitive inhibition | P. falciparum (IC5012 nM) | Brücher et al., 2012 | ||
| *4-[Hydroxy(methyl)amino]-1-(4-methoxyphenyl)-4-oxobutylphosphonic acid (Fosmidomycin reverse analog |  |
Competitive inhibition | P. falciparum (IC5020 nM) | Konzuch et al., 2014 | ||
| IspD | 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase | *L-erythritol-4-phosphate |  |
Competitive inhibition | B. abortus (IC501.36 mM) | Lillo et al., 2003 |
| 7-hydroxy-[1,2,4] triazolo [1,5-a] pyrimidine PubChem CID: 75629 (2503-56-2) |  |
Allosteric inhibition | A. thaliana (IC50140 ± 10 nM) | Witschel et al., 2011 | ||
| *6-Amino-7-(1H-benzo[d]imidazol-2-yl)-5-[5-(diethylamino)-1-methylbut-1-yl)-5H-pyrrolo [3,2-b] pyrazine-2,3-dicarbonitrile |  |
Non competitive inhibition | P. falciparum (EC50 50 nM) | Reker et al., 2014 | ||
| Pyrroloquinoxaline |  |
Non competitive inhibition | A. thaliana (IC50 1.6 μM) | Reker et al., 2014 | ||
| MMV008138 PubChem CID: 2829106 |  |
Competitive inhibition | P. falciparum (IC5047 nM) and P. vivax (IC50310 nM) | Imlay et al., 2015 | ||
| *Ethyl {3-[4-amino-5-{3-[(cyclopropylsulfonyl) amino] prop-1-yn-1-yl}-2-oxopyrimidin-1(2H)-yl] oxetan-3-yl} acetate |  |
Competitive inhibition | A. aeolicus (IC50590 ± 10 nM) | Hirsch et al., 2008 | ||
| IspE | 4-(cytidine-5-diphospho)-2-C-methyl-D-erythritol kinase | 6-(benzylthio)-2-(2-hydroxyphenyl)-4-oxo-3,4-dihydro-2H-1,3-thiazine-5-carbonitrile PubChem CID: 3768522 |  |
Competitive inhibition | E. coli (IC505.5 μM) | Tang et al., 2011 |
| *Diammonium 5′-O-{[({[2-({[5-(Dimethylamino) naphthalene-1- yl]sulfonyl}amino) ethyl] oxy}phosphinato)oxy] phosphinato} cytidine |  |
Competitive inhibition | E. coli (IC503.0 μM) | Crane et al., 2006 | ||
| IspF | 2C-Methyl-D-erythritol-2, 4-cyclodiphosphate synthase | Thiazolopyrimidine PubChem CID: 330031 |  |
Competitive inhibition | P. falciparum (IC509.6 μM) and M. tuberculosis (IC506.1 μM) | Geist et al., 2010 |
| Aryl bis sulphonamide PubChem CID: 5333 |  |
Competitive inhibition | P. falciparum (IC501.4 μM) and A. thaliana (IC50240 nM) | Thelemann et al., 2015 | ||
| Propargyl diphosphate PubChem CID: 46236597 |  |
Competitive inhibition | E. coli (IC50750 nM) | Wang et al., 2010 | ||
| IspG | 4-Hydroxy-3-methyl-2-(E)-butenyl-4-diphosphate synthase | Prop-2-yn-1-yl trihydrogen diphosphate PubChem CID: 448670 |  |
Competitive inhibition | T. thermophilus (IC50770 nM) | Quitterer et al., 2015 |
| But-3-yn-1-yl trihydrogen diphosphate PubChem CID: 46236598 |  |
Competitive inhibition | T. thermophilus (IC50580 nM) | Wang et al., 2010 | ||
| But-3-yn-1-yl trihydrogen diphosphate PubChem CID: 46236598 |  |
A. aeolicus (IC50450 nM) | ||||
| IspH | 4-Hydroxy-3-methyl-2-(E)-butenyl-4-diphosphate reductase | Pyridine phosphate PubChem CID: 10866885 |  |
Competitive inhibition | A. aeolicus (IC5035 μM) | Wang et al., 2011 |
| *(E)-4-mercapto-3-methyl but-2 enyl diphosphate (Alkyne diphosphate derivative) |  |
Competitive inhibition | E. coli (IC50210 nM) | Janthawornpong et al., 2013 | ||
*
PubChem Id not available.