International Journal of Cell Biology

Review Article

Trafficked Proteins—Druggable in Plasmodium falciparum?

Table 1

List of inhibitors known to interfere with protein trafficking or trafficked proteins in P. falciparum.


Chemical compound Structure	Chemical family	Target	Mode of action	IC₅₀ (M)	Ki (nM)	Antimalarial effect	Origin	References

	Spergualin derivate	Apicoplast protein synthesis	Suggested inhibition of chaperone-transit peptide interactions	0.15		Delayed death	Bacillus laterosporus	[7–9]
	Tetracycline derivate	Apicoplast protein synthesis	Binding to microbial ribosomes and blocking the attachment of charged aminoacyl-tRNA	10		Delayed death	Streptomyces spp	[10, 11]
	Phosphonic acid derivative	Apicoplast Isoprenoid biosynthesis	Inhibits specifically the DOXP reductoisomerase (DXR or Isp C)	0.35		Immediate	Streptomyces lavendulae	[12–14]
	Dipeptide	Aminopeptidase for example, PfM17LAP	Chelating of metal binding centres	8–21	25		Streptomyces olivoreticuli	[15–17]
	Phosphinate dipeptide analogue	Aminopeptidase for example, PfM17LAP	Proposed chelation of active site metal ions	20–75	13		Synthetic	[18, 19]
	Phosphinate dipeptide analogue	Aminopeptidase for example, PfM17LAP	Proposed chelation of active site metal ions	13–62	10		Synthetic	[18, 19]
	Hexapeptide	PM I–IV	No direct effect on haemoglobin degradation	4	PMI: 0.4 PMII: 0.03 PMIII: 0.1 PMIV: 0.3		Actinomyces	[20, 21]
	Peptidomimetic	PM II	Mimic Phe-Leu found in haemoglobin alpha chain	0.04	0.5		Synthetic	[22–24]
	Peptidomimetic	PM I, II, IV		n.d.	I: 21 ii: 25 IV: 46	Expanded lifespan of mice (up to 171%)	Synthetic	[25]
	Peptidomimetic	PMII		0.1		Expanded lifespan of mice (up to 161%)	Synthetic	[25]
	Aryl amino alcohol	Not precisely known, but effective against plasmepsin I–III		0.001–0.006			Classical antimalarial drug with unknown mode of action, developed as synthetic quinine analogue	[25–27]
	Peptidomimetic	PMV	Inhibits the PMV cleavage of a PEXEL peptide	70			HIV protease inhibitor	[25]
	Peptidomimetic	PMV	Inhibits the PMV cleavage of a PEXEL peptide	n.d.			HIV protease inhibitor	[25]
	Peptidomimetic	PMV	Inhibits the PMV cleavage of a PEXEL peptide	15			HIV protease inhibitor	[25]
	Peptidomimetic	PMV	Inhibits the PMV cleavage of a PEXEL peptide	n.d.			HIV protease inhibitor	[25]

The given IC₅₀ values refer to the cellular level. Not yet determined: n.d.