Table 1.

Antiribosomal activities and selectivities of 4,5-AGA derivatives^[a]

		IC50 (μM)				Selectivity
Compound	4”-Substituent	wt	Mit13	A1555G	Cyt14	Mit13	A1555G	Cyt14
Neomycin series (6 basic amines in parent)
Neomycin, 4	CH2OH	0.034	3.6	0.40	34	106	12	1000
27	H	0.038	5.0	0.077	32	132	2	865
31	CH3	0.039	10.7	0.945	32	274	24	821
34	CH2NH2	0.025	14	0.470	32	560	19	1391
35	CH2NHCHO	0.048	15	1.09	56	313	23	1167
36	CH2NHAc	0.038	18	1.2	38	474	32	1000
Paromomycin series (5 basic amines in parent)
Paromomycin, 3	CH2OH	0.033	131	12	37	3970	364	1121
40	H	1.059	-	-	-	-	-	-
46	CH3	1.092	-	-	-	-	-	-
49	CH2NH2	0.090	36	6.3	6.6	400	70	73
51	CH2NHCHO	0.040	166	27	114	4140	675	2850
52	CH2NHAc	0.513	-	-	-	-	-	-
53	CH2NHCONH2	0.096	114	45	184	1188	469	1917
Propylamycin series (5 basic amines in parent)
Propylamycin, 19	CH2OH	0.022	150	56	61	6818	2545	2773
20	CH2NH2	0.14	62	38	9.0	443	271	64
21	CH2NHCHO	0.034	505	118	175	14853	3471	5147
22	CH2NHCONH2	0.078	318	189	194	4077	2423	2487
Ribostamycin series (4 basic amines in parent)
Ribostamycin, 6	CH2OH	0.089	461	86	416	5180	966	4674
57	H	1.612	-	-	-	-	-	-
64	CH2NH2	0.088	76	34	50	861	386	570
66	CH2NHCHO	0.686	-	-	-	-	-	-
67	CH2NHAc	3.542	-	-	-	-	-	-
Apralog series (5 basic amines in parent)
14	CH2OH	0.16	439	272	475	2815	1745	3045
15	H	0.128	332	211	444	2594	1648	3469
79	CH3	0.28	562	323	462	2022	1162	1662
16	CH2NH2	0.12	113	81	111	941	675	925
75	CH2NHCHO	0.31	572	232	567	1863	755	1847
Advanced Apralog series (6 basic amines in parent)
17	CH2OH	0.071	68	13	190	957	183	2676
18	CH2NH2	0.030	42	20	38	1400	667	1267
76	CH2NHCHO	0.085	93	11	142	1096	130	1669

^[a]All values were determined in at least duplicate using 2.5-fold dilution series