. Author manuscript; available in PMC: 2012 Sep 8.

Published in final edited form as: J Med Chem. 2011 Aug 5;54(17):6014–6027. doi: 10.1021/jm200454y

Table 3.

Biological Evaluation of Benzo[b]furans II


entry	cmpnd	R¹	R²(D-ring)	tubulin^a IC₅₀ (μM)	MCF-7^b IC₅₀ (nM)	activated HUVEC^c IC₅₀ (nM)	quiescent HUVEC^d IC₅₀ (nM)	selectivity ratio^e
1	4	-	-	1.8 ± 0.2	2.9	3.6	3.9	1.1
2	12	H		1.3 ± 0.2	39 ± 18	45	41	0.9
3	21	H		1.3 ± 0.04	42 ± 10	41	32	0.8
4	25	H		1.9 ± 0.4	26±5	32	44	1.4
5	26	H		2.3 (both runs)	48 ± 10	30	34	1.1
6	31a	H	H	1.6 ± 0.2	55 ± 5	45	63	1.4
7	31b	OH	H	ND	45 ± 15	83	322	3.9
8	27	OH		0.8 ± 0.2	4.0 ± 0.1	1.7	3.4	2.0
9	8	OH	Me	3.0 ± 0.6	2.4 ± 2	0.31	25	81
10	28	OH		1.3 ± 0.07	1.0 ± 0.5	0.4	0.7	1.8
11	24	OiPr		ND	42 ± 6	665	419	0.6
12	33a	H	Br	ND	495 ± 25	510	309	0.6
13	35	H		ND	71 ± 1	45	27	0.6
14	45	H		ND	215 ± 15	484	405	0.8
15	36	OH		8.7 ± 0.8	0.6 ± 0.2	3.6	3.4	0.9
16	37	OH		ND	0.5 ± 0.2	0.31	0.36	1.2
17	42	OH		ND	ND	2.6	3.3	1.3
18	39	OH		ND	ND	0.38	2.3	6.0
19	43	OH	CN	ND	ND	1.1	3.0	2.7
20	40	OH		ND	ND	2.6	2.3	0.9
21	46	OH		ND	ND	29	36	1.2
22	47	OH		ND	ND	3.1	2.9	0.9
23	49	OH	NH₂	ND	ND	1.9	8.8	4.6

The tubulin concentration was 10 μM. Inhibition of extent of assembly was the parameter measured (n = 2).

Cells were grown for 48 h at 37 °C in a humidified 5%CO₂ atmosphere. Cell protein was the parameter measured. At least two independent experiments were performed with each compound.

For activated growth conditions HUVEC cells were seeded at 2500 and 500 cells/well, respectively, and cultured in EGM-2 medium (Lonza) or F12K medium containing 0.03 mg/mL endothelial cell growth supplement.

For quiescent growth conditions HUVEC and HAAE-1 cells were seeded at 15 000 and 5000 cells/well, respectively, in basal medium (EBM-2 or F12K) containing 0.5% fetal calf serum and antibiotics.

Selectivity ratio (IC₅₀ quiescent)/(IC₅₀ activated).