Table 1.

Inhibition of Tubulin Polymerization, Growth of MCF-7 Human Breast Carcinoma Cells and Colchicine Binding by Compounds 3–45 and Reference Compound 2

compd	R1	R2	X	tubulina IC50 ± SD (μM)	MCF-7b IC50 ± SD (nM)	inhibition colchicine bindingc (% ± SD)
3	H	H	S	2.6±0.2	34±9	68±0.8
4	H	H	C=O	3.5±0.07	150±50	26±0.3
5	H	H	CH2	28±2	nd	nd
6	COOMe	H	S	2.9±0.1	25±1	74±2
7	COOMe	H	C=O	2.7±0.3	33±10	49±10
8	COOMe	H	CH2	4.2±0.02	190±70	33±7
9	COOEt	H	S	2.9±0.2	40±2	19±7
10	COOEt	H	C=O	2.6±0.3	80±20	51±6
11	COOEt	H	CH2	5.4±1	nd	nd
12	H	5-Cl	S	2.6±0.2	77±7	51±4
13	H	5-C1	C=O	2.5±0.5	53±10	44±9
14	H	5-Cl	CH2	24±2	nd	nd
15	COOMe	5-Cl	S	2.5±0.3	42±10	73±0.2
16	COOMe	5-Cl	C=O	1.6±0.1	30±6	61±4
17	COOMe	5-Cl	CH2	1.7±0.5	87±30	49±4
18	COOEt	5-Cl	S	2.2±0.2	110±2	53±3
19	COOEt	5-Cl	C=O	1.4±0.2	110±10	49±3
20	COOEt	5-Cl	CH2	2.5±0.5	230±60	39±4
21	COOEt	5-Cl	COCH2	>40	nd	nd
22	COOEt	5-Cl	COCO	>40	nd	nd
23	COOEt	5-Cl	CH2CH2	>40	nd	nd
24	H	5-Br	S	1.6±0.3	43±7	65±3
25	H	5-Br	C=O	1.9±0.3	60d	45±5
26	H	5-Br	CH2	13±0.8	nd	nd
27	COOMe	5-Br	S	0.99±0.1	33±10	75±3
28	COOMe	5-Br	C=O	1.3±0.08	18±4	67±4
29	COOMe	5-Br	CH2	1.3±0.08	30±9	59±7
30	COOEt	5-Br	S	1.6±0.2	83±20	62±7
31	COOEt	5-Br	C=O	1.6±0.05	67±10	58±2
32	COOEt	5-Br	CH2	1.7±0.2	100d	53±4
33	H	5-OMe	S	4.1±0.6	22±2	61±4
34	H	5-OMe	C=O	3.4±0.4	200d	32±7
35	H	5-OMe	CH2	14±0.5	nd	nd
36	COOMe	5-OMe	S	2.0±0.2	13±3	93±0.8
37	COOMe	5-OMe	S=O	>40	nd	nd
38	COOMe	5-OMe	S(=O)2	>40	nd	nd
39	COOMe	5-OMe	C=O	0.67±0.02	17±6	78±6
40	COOMe	5-OMe	CHOH	>40	nd	nd
41	COOMe	5-OMe	CH2	1.4±0.2	33±10	59±1
42	COOEt	5-OMe	S	2.4±0.2	46±3	71±2
43	COOEt	5-OMe	C=O	2.6±0.04	90±10	49±4
44	COOEt	5-OMe	CHOH	>40	nd	nd
45	COOEt	5-OMe	CH2	2.8±0.3	93±10	42±4
2				1.1±0.1	2.5±0.6	99±0.7

^aInhibition of tubulin polymerization. Tubulin was 10 μM during polymerization.

^bInhibition of growth of MCF-7 human breast carcinoma cells.

^cInhibition of [³H]colchicine binding. Tubulin was at 1 μM, both [³H]colchicine and inhibitor were at 5 μM.

^dSame value obtained in all experiments.