Table 3.

Effects of selenophene-core compounds on the transcriptional activities of Estrogen Receptor^a and antiproliferative activity in MCF-7 cells.

series	entry	cmpd	Agonist Modeb				Antagonist Modec, d				MCF-7Inhibition(%)e	VEROIC50 (μM)f
			ERα		ERβ		ERα		ERβ
			EC50 (μM)	Eff (%E2)	EC50 (μM)	Eff (%E2)	IC50 (μM)	Eff (%E2)	IC50 (μM)	Eff (%E2)
I	1	2a	-	16 ± 2	-	11 ± 4	0.52	44 ± 10	0.028	35 ± 4	0	16.6 ± 3.89
	2	2b	1.36	157 ± 12	0.079	82 ± 7	-	96 ± 13	0.3	50 ± 11	3.4	>50g
	3	2c	-	33 ± 6	-	24 ± 3	-	103 ± 28	-	98 ± 14	9.3	>50
	4	2d	-	12 ± 4	-	38 ± 6	-	148 ± 2	-	86 ± 13	0	>50
	5	2e	-	−7 ± 3	0.434	60 ± 4	0.425	−22 ± 8	5.391	66 ± 3	19.3	>50
	6	2f	0.23	68 ± 2	0.17	71 ± 1	-	59 ± 10	-	91 ± 6	10.5	>50
	7	2g	1.28	44 ± 13	-	14 ± 5	-	73 ± 8	-	74 ± 5	19.6	>50
	8	2h	0.04	49 ± 3	-	22 ± 8	-	100 ± 14	−0.25	51 ± 16	5.3	>50
	9	2i	-	25 ± 8	0.13	55 ± 5	-	75 ± 7	-	89 ± 6	17.9	>50
	10	2j	-	25 ± 8	0.15	42 ± 10	0.72	68 ± 2	-	79 ± 3	4.4	>50
II	11	4a	-	7 ± 3	-	16 ± 7	-	57 ± 2	0.475	49 ± 9	0	>50
	12	4b	-	19 ± 4	0.034	62 ± 8	-	80 ± 10	-	94 ± 10	0	>50
	13	4c	0.32	32 ± 8	1.147	54 ± 10	-	46 ± 9	0.341	50 ± 5	0	>50
	14	4d	-	21 ± 6	-	21 ± 3	-	33 ± 6	0.001	10 ± 7	0	>50
	15	4e	-	35 ± 5	-	17 ± 2	-	67 ± 3	-	58 ± 6	0	>50
III	16	6a	0.015	69 ± 11	0.013	40 ± 5	-	161 ± 22	2.53	75 ± 4	0	>50
	17	6b	0.79	21 ± 5	0.009	69 ± 9	-	93 ± 11	2.96	25 ± 8	2.5	>50
	18	6c	-	−3 ± 1	0.441	46 ± 1	1.33	8 ± 1	0. 51	21 ± 5	26.1	>50
	19	6d	-	16 ± 4	-	15 ± 6	1.58	26 ± 2	-	18 ± 13	26.5	>50
	20	6e	-	−23 ± 3	-	27 ± 2	0.561	19 ± 2	-	125 ± 20	11.3	>50
	21	6f	0.12	226 ± 28	0.3	31 ± 7	-	127 ± 42	-	69 ± 16	0	>50
	22	6g	-	73 ± 9	-	50 ± 3	-	87 ± 6	-	59 ± 8	8.1	>50
IV	23	8a	-	−4 ± 3	-	12 ± 3	10.4	−7 ± 2	0.111	23 ± 3	29.6	>50
	24	8b	0.32	112 ± 29	0.033	77 ± 8	-	104 ± 29	-	82 ± 2	16.6	>50
	25	8c	0.27	74 ± 4	0.017	69 ± 5	0.87	27 ± 1	-	79 ± 7	75.3	>50
	26	8d	1.8	148 ± 2	0.061	73 ± 14	-	74 ± 19	-	91 ± 8	18.6	>50
	27	4OHT	0.008	35 ± 3	-	−1 ± 1	0.003	35 ± 3	0.001	−20 ± 2	81.7	15.1 ± 5.2

^aLuciferase activity was measured in HEK293T cells transfected with 3 × ERE-driven luciferase reporter and expression vectors encoding ERα or ERβ and treated in triplicate.

^bIn the agonist mode, increasing concentrations of compounds alone (up to 10⁻⁵ M) are given. EC₅₀ values and standard deviations (mean ± SD from three replicates) represent the concentrations producing 50% of the maximal response to the compound on ERα or ERβ. Eff (% E₂) is the maximal response to the compound as a percentage of the response to 10⁻⁸ M 17β-estradiol (E₂).

^cIn the antagonist mode, increasing concentrations of compounds (up to 10⁻⁵ M) are given together with a maximally stimulating dose of E₂ (10⁻⁸ M). IC₅₀ values and standard deviations (mean ± SD from three replicates) represent the concentrations that reduce the E₂ response by 50%. Eff (% E₂) is the response to the compound at the highest concentration as a percentage of the activity of 10⁻⁸ M 17β-estradiol (E₂).

^dERs have considerable basal activity in HEK293T cells; compounds with inverse agonist activity are given negative efficacy values. Omitted EC₅₀ or IC₅₀ values were too high to be determined accurately; omitted Eff (%E₂) values were too low to be accurately determined.

^eRelative inhibition rate of antiproliferative potencies determined by MTT assays. The final concentration of the compounds is 10 μM.

^fIC₅₀ values are an average of at least three independent experiments ± standard deviation (mean ± SD).

^gIC₅₀ not determinable up to highest concentrations tested.