Table 2.

Summary of medicinal chemistry studies

Compound	Authors	Target	Chemical class	Lowest IC50 (strain)
6	Sperandeo and Brun [[66]]	-	Pyrazolylnaphthoquinones, 5-aminoisoxazole	0.11 μg/mL (K1)
7	Silva et al. [67]	-	1,4-naphthoquinones	0.03 μM (FcB1)
8	Charris et al. [68]	β-haematin	Thieno(2,3-b)quinoline	74.42%1
9	Cunico et al. [69]	Aspartyl protease	Hydroxyethylpiperazines	4.6 μM (3D7)
10	Cunico et al. [70]	Aspartyl protease	Hydroxyethyylpiperazines	5.1 μg/mL (W2)
11	Gnoatto et al. [71]	β-haematin	Piperazine, 3-acetylursolic acid	0.08 μM (FcB1)
12	de Sá et al. [72]		Betulinic acid	5.99 μM (W2)
13	Pinheiro et al. [73]	-	Sesquiterpenes	0.05 ng/mL (P. falciparum mefloquine resistant)
14	Barbosa et al. [74]	-	Ozonides	13.6 μg/mL
15	Oliveira et al. [75]	Cysteine proteases	Semicarbazone, Thiosemicarbazone	7.2 μM (W2)
16	Camacho et al. [76]	β-haematin	Benzimidazole-5-carbohydrazides	8.43 μM
17	Corrales et al. [77]	Hypoxanthine-guanine phosphoribosyltransferase	6-thiopurine Steroids	82%1
18	Barazarte et al. [78]	β-haematin	Pyrazolo and pyrimido benzothiazine dioxide	92.32%2
19	Barazarte et al. [79]	β-haematin	Benzothiazines	78.17%2
20	Vellasco Junior et al. [80]	Aspartyl protease	Thioetherhydroxyethyl, Sulfonamides	15 μM (W2)
21	Dominguez et al. [81]	β-haematin	Chlorovinyl sulfones	0.025 μM (W2)
22	Dominguez et al. [82]	β-haematin	Sulfonamide chalcones	0.48 μM (W2)
23	León et al. [83]	Glucose metabolism β-haematin	Sulfonylureas	1.2 μM (W2)
24	Arancibia et al. [84]	β-haematin	Rhenium bioorganometalics, Aminoquinoline	0.048 μM (3D7)
25	Rojas Ruiz et al. [85]	β-haematin	Aminoquinolines, thiazolidinone	0.25 μM (3D7)
26	Charris et al. [86]	β-haematin	E-2-quinolinylbenzo-cycloalcanones	90%3
27	Vashist et al. [87]	β-haematin	Quinolone, 6-thiopurine	inactive
28	de Souza et al. [88]	β-haematin	4-aminoquinolines, platinum (II) complexes	84 %4
29	Cunico et al. [89]	β-haematin	4-aminoquinolines	1.39 μg/mL (W2)
30	Rodrigues et al. [90]	β-haematin	Quinoline	Active
31	Domínguez et al. [91]	Cysteine protease falcipain	Quinolinyl chalcones	19 μM (FcB1)
32	Ferrer et al. [92]	β-haematin	Chloroquinolines	94.93%3
33	Navarro et al. [93]	β-haematin	Gold-chloroquine complexes	−5
34	Domínguez et al. [94]	Cysteine protease β-haematin	Phenylurenyl chalcones	1.76 μM
35	de Andrade-Neto et al. [95]	-	Naphthoquinones, Phenazines	1.67 μM (W2)
36	Hilário et al. [96]	-	3-alkylpyridines alkaloids	<3.38 μM (W2)
37	Rodrigues et al. [97]	β-haematin	Bisquinoline	56.76 %2

¹ Percentage of inhibition of parasite growth (P. berghei in mice) at day 9 (dose: 10 mg/kg).

² Inhibition of globin proteolysis (IGP) expressed as percentage.

³ Inhibition of β-haematin synthesis (IβHS) expressed as percentage.

⁴ Inhibition of parasite multiplication on days (dose: 25 mg/kg).

⁵ Activity expressed as IC₅₀(CQDP)/IC₅₀(complex).