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.