Synthesis, SAR, and Docking Studies Disclose 2-Arylfuran-1,4-naphthoquinones as In Vitro Antiplasmodial Hits
Table 2
In vitro antiplasmodial activity (IC50) against Plasmodium falciparum (W2), cytotoxicity (CC50, Hep G2A16 cells), selectivity index (SI), and binding energy values of docking simulations for 4PD4 and 5FI8 with naphthoquinones 6a–h, 7a–h, and 8a–h.
Compound
IC50 (μmol⋅L−1
CC50 (μmol⋅L−1
Binding energy 4PD (Kcal⋅mol−1)
Binding energy 5FI (Kcal⋅mol−1)
6a
99.85 8.46
970.00 42.60
9.72
−8.2
−8.2
6b
59.24 10.27
138.97 15.14
2.34
−8.5
−8.5
6c
52.65 3.71
146.80 29.10
2.79
−8.5
−8.7
6d
90.17 10.43
21.55 9.44
0.24
−8.5
−9.0
6e
72.21 2.98
1,127.00 39.67
15.61
−8.9
−9.0
6f
45.76 2.55
19.51 4.03
0.43
−9.4
−10.2
6g
110.34 6.64
940.30 40.10
8.52
−10.3
−10.7
6h
39.55 8.98
335.90 26.70
8.49
−10.6
−9.1
7a
23.22 5.09
4.68 0.70
0.20
−8.6
−9.1
7b
25.10 2.64
11.91 4.65
0.47
−8.6
−9.1
7c
24.70 2.25
11.53 2.97
0.47
−8.5
−9.2
7d
50.22 2.90
12.99 2.01
0.26
−8.6
−9.3
7e
26.41 3.12
21.33 3.15
0.80
−9.2
−9.3
7f
23.44 6.39
13.68 4.46
0.58
−9.9
−10.2
7g
40.72 7.82
6.10 0.84
0.15
−10.2
−9.9
7h
19.91 4.35
68.68 14.79
3.45
−10.0
−9.8
8a
26.57 3.25
869.10 32.71
32.71
−8.2
−8.9
8b
28.86 3.66
12.51 2.18
0.43
−8.4
−9.0
8c
11.65 2.50
115.90 21.90
9.94
−8.3
−9.1
8d
23.77 2.41
119.20 23.70
5.01
−8.4
−9.5
8e
30.55 3.81
143.27 12.24
4.69
−8.9
−9.4
8f
18.78 0.83
97.89 13.22
5.21
−9.90
−11.5
8g
21.80 2.64
120.84 6.05
5.54
−10.0
−11.3
8h
140.70 7.80
1,048.90 32.90
2.40
−10.3
−10.5
2
206.38 3.64
1567.96 7.44
7.6
ND
ND
0.280 0.01
361.84 10.64
1,292.30
ND
ND
: chloroquine; : concentration (μmol⋅L−1) that kills 50% of P. falciparum, determined by the pLDH method; : concentration that kills 50% of Hep G2A16 cells 24 h after incubation with the compounds, determined by the MTT method; (selectivity index): CC50/IC50; : cytochrome bc1 complex subunit 1; : dihydroorotate dehydrogenase; ND: not determined.