TABLE 3 .

Interaction of 4′-O-alkyl derivatives with eukaryotic drug binding pockets

Drug	IC50 (mg/liter) with eukaryotic A sites in the ribosomea:
	Mitochondrial wild-type	Mitochondrial mutant A1555G	Cytosolic wild-type	Rabbit reticulocytes
Paromomycin	50.66 ± 13.33	5.77 ± 2.32	9.89 ± 2.73	9.55 ± 4.94
4′ Deoxy paromomycin	74.1 ± 12.4	24.2 ± 10.5	28.4 ± 13.8	17.3 ± 4.2
4′,6′-O-(3-Phenylpropylidene) paromomycin	305.7 ± 74.1	126.9 ± 54.4	150.5 ± 28.0	ND
4′-O-(3-Phenylpropyl) paromomycin	49.85 ± 15.39	105.68 ± 39.23	268.57 ± 54.97	ND
Compound 13	109.02 ± 6.73	81.11 ± 8.77	92.32 ± 9.20	49.74 ± 3.48
Compound 12	149.54 ± 38.62	148.36 ± 30.59	161.48 ± 13.93	49.83 ± 5.47
Compound 11	194.88 ± 57.17	151.92 ± 31.44	165.52 ± 28.30	59.93 ± 30.10
Compound 14	102.39 ± 9.99	90.88 ± 9.96	125.18 ± 3.07	49.98 ± 16.75
Compound 10	96.82 ± 4.22	119.83 ± 45.62	94.65 ± 30.97	37.58 ± 14.14
Compound 22	206.31 ± 112.31	98.00 ± 39.68	126.41 ± 71.71	37.40 ± 4.61
Compound 9	106.58 ± 24.30	174.76 ± 46.48	128.22 ± 27.65	40.92 ± 8.39
Compound 21	325.05 ± 123.72	252.74 ± 37.61	240.92 ± 69.84	130.03 ± 41.37
Compound 16	87.49 ± 30.97	81.35 ± 17.06	74.36 ± 11.94	24.00 ± 5.10
Compound 15	>700	>700	>700	374.34 ± 117.07
Compound 17	31.84 ± 14.21	24.32 ± 3.30	25.54 ± 2.30	8.81 ± 4.42
Compound 18	68.24 ± 5.66	46.90 ± 4.07	89.83 ± 4.87	43.10 ± 1.88
Compound 19	504.69 ± 107.23	288.80 ± 10.81	171.37 ± 22.52	91.19 ± 18.69
Compound 20	>700	>700	482.63 ± 58.51	90.97 ± 8.00

^aThe interaction of 4′-O-alkyl derivatives with the eukaryotic drug binding pocket is measured by the drug concentrations (in milligrams per liter) required to inhibit in vitro synthesis of functional firefly luciferase to 50% (IC₅₀s). The values are means ± standard deviations (SD) for experiments performed in triplicate. ND, not determined.