Table 3.

Efficiency of compounds for internal targeting.

Target	Parasite species	Compound name	Effect on protein	Effect on parasite	Cell stage in vitro	Effect in vivo	Host species	Reference
ATP6/SERCA	P. falciparum	Artemisinin	–	IC50 11 – 13 nM	Trophozoites	–	–	del Pilar Crespo et al., 2008
	T. gondii		Inhibition at 10 μM	IC50 0.36–8 μM	Tachyzoites	–	–	Berens et al., 1998; Jones-Brando et al., 2006; Nagamune et al., 2007; Hencken et al., 2010
	Trypanosoma spp.		–	IC50 13–20 μM	Trypomastigotes/Epimastigotes	–	–	Yang and Liew, 1993; Mishina et al., 2007; Sen et al., 2010
	Leishmania spp.		–	IC50 0.75–120 μM	Promastigotes/Amastigotes	Reduction of parasite burden with oral dose of 10 mg kg−1	Mouse/Hamster
	B. gibsoni		–	IC50 2.2 μM	Trophozoites	–	–	Iguchi et al., 2015
	P. falciparum	Arterolane	Ki 7.7 μM	IC50 1.5 nM	Trophozoites	–	–	Abiodun et al., 2013
	P. falciparum	Thapsigargin	–	IC50 0.25– 0.30 μM	Trophozoites	–	–	del Pilar Crespo et al., 2008; Abiodun et al., 2013
	T. gondii		Inhibition at 1 μM	–	–	–	–	Nagamune et al., 2007
	Trypanosoma spp.		–	IC50 30–34 μM	Trypomastigotes/Epimastigotes	–	–	Mishina et al., 2007
	L. donovani		–	28.1 μM	Promastigotes	–	–	Mishina et al., 2007
	E. invadens		–	Inhibition of encystation at 0.5 μM	Trophozoites	–	–	Martínez-Higuera et al., 2015
	N. canium		–	Growth Inhibition at 0.1 μg ml−1	Tachyzoites	–	–	Kim et al., 2002
Cytochrome bc1 complex	P. falciparum	Atovaquone	IC50 0.2 nM	IC50 2 nM	Trophozoites	–	–	da Cruz et al., 2012
	T. gondii		–	IC50 0.1–0.5 μM	Tachyzoites	IC50 0.14–0.85 μM	Mouse	Doggett et al., 2012
	Babesia spp.		–	IC50 94 nM	Trophozoites	Effective at dose of 100 mg kg−1 d−1	Hamster	Hughes and Oz, 1995; Wittner et al., 1996; Matsuu et al., 2008
			–	–	–	Effective at dose of 1500 mg d−1 plus azithromycin 500 mg on day 1 and 250 mg per day thereafter	Human	Krause et al., 2000
	L. donovani		–	–	–	30 % reduction of parasite burden with 100 mg kg−1 for 5 days	Mouse	Croft et al., 1992
	Theileria spp.	Buparvaquone	–	–	–	Effective at 2.5–6 mg kg−1	Cattle, Horse	McHardy et al., 1985; Zaugg and Lane, 1989; Muraguri et al., 1999; Mhadhbi et al., 2010
	Leishmania spp.		–	IC50 0.001–5.495 μM	Promastigotes/Amastigotes	60% reduction of parasite burden with 100 mg kg−1 for 5 days	Mouse	Croft et al., 1992; Mäntylä et al., 2004a; Reimão et al., 2012; Jamal et al., 2015
	P. falciparum	Decoquinate	IC50 2 nM	IC50 2.6–36 nM	Trophozoites	–	–	da Cruz et al., 2012
	P. falciparum	WR249685	–	IC50 3 nM	Trophozoites	–	–	Biagini et al., 2008
	P. falciparum	TCMDC-135546	–	IC50 22 nM	Trophozoites	–	–	Raphemot et al., 2015
Mitochondrial F1F0 ATPase	T. brucei	Furamidine (DB75)	Inhibition at 10 μM	IC50 4.5 nM	Trypomastigotes	Effective as pentamidine at 3 mg kg−1 d−1, for 7 days	Gerbil	Steck et al., 1982; Ismail et al., 2003; Lanteri et al., 2008
		Pafuramidine (DB289)	–	IC50 14.6 μM	Trypomastigotes	Effective at a dose of 400 mg kg−1 p.o.	Mouse	Ansede et al., 2004
		DB820	–	IC50 7.9–141 nM	Trypomastigotes	Effective at 10 mg kg−1 i.p.	Mouse	Wenzler et al., 2009
		DB829	–	IC50 20–346 nM	Trypomastigotes	Effective at 10 mg kg−1 i.p.	Mouse	Wenzler et al., 2009
Mitochondrial choline transporter	P. falciparum	G25	–	–	–	–	–	Wengelnik et al., 2002; Biagini et al., 2004
	T. brucei		–	EC98 0.16 μM	Trypomastigotes	–	–	de Macêdo et al., 2015
VPPase VP1	T. gondii	AMDP	IC50 0.9 μM	Inhibition at 5–10 μM	–	–	–	Drozdowicz et al., 2003
CRT	P. falciparum	Verapamil	IC50 30 μM	–	–	–	–	Ye and van Dyke, 1994
		Quinine	IC50 48 μM	–	–	–	–	Martin et al., 2009
		Saquinavir	IC50 13 μM	–	–	–	–	Martin et al., 2012
		Dibemethin 6a	IC50 69 μM	IC50 26 nM	Trophozoites	–	–	Zishiri et al., 2011
MDR1	P. falciparum	ACT-213615	–	IC50 4 nM	Trophozoites	ED90 8.4 mg kg−1 as effective as chloroquine	Mouse	Brunner et al., 2012, 2013
		ACT-451840	–	IC50 4 nM	Gametocytes	IC50 2.7 ng ml−1 (3.6 nM)	Human	Krause et al., 2016; Le Bihan et al., 2016; Ng et al., 2016