Table 1.

Inhibitory effects on the proliferation of tumor cell lines in cell culture. IC₅₀ = 50% inhibitory concentration.

Compd	Nucleoside	AA	R	IC50 (μM)
				L1210	L1210/TK−	CEM	CEM/TK−	HeLa	HeLa/TK−	Caco-2	Colo-320
2	d4T	–	–	8.9 ± 3.2c	≥250	≥250	>250	>250	>250	>250	159 ± 36
16	d4T	l-Ala	Bn	8.9 ± 0.4c	7.4 ± 4.6	92 ± 0	46 ± 21	116 ± 54	29 ± 7	241 ± 13	133 ± 18
17	d4T	l-Ala	cHex	29 ± 5	25 ± 3	73 ± 9	54 ± 17	96 ± 0	36 ± 9	135 ± 7	56 ± 24
18	d4T	l-Ala	${\mathrm{CH}}_2^t\mathrm{Bu}$	47 ± 4	23 ± 6	96 ± 3	37 ± 2	110 ± 35	53 ± 23	174 ± 72	30 ± 16
3	ddA	–	–	>250	–	>250	–	>250	–	–	–
19	ddA	l-Ala	${\mathrm{CH}}_2^t\mathrm{Bu}$	76 ± 3	–	36 ± 4	–	35 ± 5	–	–	–
5	3TC	–	–	>250	>250	>250	>250	>250	>250	>250	>250
6	N-Acetyl-3TC	–	–	>250	>250	>250	>250	242 ± 11	>250	>250	>250
22 a	3TC	l-Ala	Bn	>250	>250	>250	155 ± 38	>250	>250	>250	>250
23 b	3TC	l-Ala	Bn	>250	150 ± 18	214 ± 50	139 ± 67	>250	256 ± 21	>250	>250
24	N-Acetyl-3TC	l-Ala	Bn	121 ± 6	–	120 ± 2	–	155 ± 61	–	>250	>250
25	3TC	l-Ala	Bn	86 ± 23	57 ± 6	116 ± 9	106 ± 18	93 ± 16	38 ± 7	87 ± 44	85 ± 50
11	ABC	–	–	>250	–	>250	–	170 ± 1	–	–	–
34	ABC	l-Ala	Bn	54 ± 2	–	19 ± 0	–	23 ± 6	–	–	–
35	ABC	l-Ala	${\mathrm{CH}}_2^t\mathrm{Bu}$	48 ± 5	–	27 ± 2	–	36 ± 17	–	–	–
13	AICA	–	–	>250	–	210 ± 56	–	165 ± 18	>250	–	–
38	AICA	l-Ala	Bn	>250	–	>250	–	>250	>250	–	–
39	AICA	l-Ala	Me	>250	–	>250	–	>250	>250	–	–
40	AICA	l-Ala	${\mathrm{CH}}_2^t\mathrm{Bu}$	>250	–	>250	–	>250	>250	–	–

Data represent the mean ± SD of at least 2 to 3 independent experiments.

^aPhosphorotetraamidate.

^bN-Phosphorodiamidate.

^cNo dose response.