Table 8.
Synthesized compound antiproliferative activity and selectivity index against hormone-dependent MCF-7, hormone-independent MDA-MB-231 breast cancer cell lines, normal MRC-5 human lung tissue fibroblasts cell lines, and Ishikawa endometrial adenocarcinoma cell lines, as well as the downregulation of ERα in MCF-7 and PR antagonism in MCF-7 cell lines.
| Comp. | MCF-7 a | MDA-MB-231 b | SI c | MRC-5 d | MCF-7 DR e | PR MCF-7 f | Ishikawa g |
|---|---|---|---|---|---|---|---|
| (IC50 nM) | (IC50 nM) | (IC50 nM) | (IC50 nM) | (IC50 nM) | (IC50 nM) | ||
| 3DPQ-1 | 0.76 ± 0.24 h,‡,§ | 72.44 ± 0.32 ‡,§ | 95.31 ‡,§ | >100 | >100 | >100 | 0.94 ± 0.36 g,‡,§ |
| 3DPQ-2 | 0.73 ± 0.42 ‡,§ | 72.42 ± 0.47 ‡,§ | 99.20 ‡,§ | >100 | >100 | >100 | 0.99 ± 0.35 ‡ |
| 3DPQ-3 | 0.61 ± 0.56 ‡,§ | 86.63 ± 0.68 ‡,§ | 142.02 ‡,§ | >100 | >100 | >100 | 0.84 ± 0.74 ‡,§ |
| 3DPQ-4 | 0.64 ± 0.15 ‡,§ | 67.31 ± 0.34 ‡,§ | 105.17 ‡,§ | >100 | >100 | >100 | 0.92 ± 0.43 ‡,§ |
| 3DPQ-5 | 1.02 ± 0.64 ‡,§ | 52.64 ± 0.69 ‡,§ | 51.61 ‡,§ | >100 | >100 | >100 | 1.42 ± 0.32 ‡,§ |
| 3DPQ-6 | 1.14 ± 0.49 ‡,§ | 52.31 ± 0.46 ‡,§ | 45.89 ‡,§ | >100 | >100 | >100 | 1.46 ± 0.43 ‡,§ |
| 3DPQ-7 | 0.78 ± 0.52 ‡,§ | 51.96 ± 0.68 ‡,§ | 66.61 ‡,§ | >100 | >100 | >100 | 1.74 ± 0.43 ‡,§ |
| 3DPQ-8 | 1.06 ± 0.45 ‡,§ | 42.56 ± 0.35 ‡,§ | 40.15 ‡,§ | >100 | >100 | >100 | 1.98 ± 0.32 ‡,§ |
| 3DPQ-9 | 0.62 ± 0.15 ‡,§ | 81.63 ± 0.42 ‡,§ | 131.66 ‡,§ | >100 | >100 | >100 | 0.89 ± 0.24 ‡,§ |
| 3DPQ-10 | 0.97 ± 0.34 ‡,§ | 41.97 ± 0.32 ‡,§ | 42.27 ‡,§ | >100 | >100 | >100 | 1.55 ± 0.42 ‡,§ |
| 3DPQ-11 | 0.81 ± 0.22 ‡,§ | 67.12 ± 0.54 ‡,§ | 82.86 ‡,§ | >100 | >100 | >100 | 1.37 ± 0.47 ‡,§ |
| 3DPQ-12 | 0.56 ± 0.11 ‡,§ | 82.84 ± 0.61 ‡,§ | 147.93 ‡,§ | >100 | >100 | >100 | 0.77 ± 0.43 ‡,§ |
| E2 i | N m | NA | NA | NA | NA | NA | NA |
| 4-OHT. j | 1.19 ± 0.57 § | 37.10 ± 0.45 § | 31.18 § | >10 | >100 | >100 | 1.29 ± 0.43 § |
| Ral. k | 0.90 ± 0.19 ‡ | 93.41 ± 0.48 ‡ | 103.97 ‡ | >10 | >100 | >100 | 0.97 ± 0.35 ‡ |
| Control l | NA | NA | NA | NA | NA | NA | NA |
a Concentration that prevents the growth of 50% of MCF-7 cell lines; b Concentration that prevents the growth of 50% of MDA-MB-231 cell lines; c Selectivity index toward the cell line: [IC50(MDA-MB-231)]/[IC50(MCF-7)] for the antiproliferative effect of both designed compounds and reference compounds; d Concentration that prevents the growth of 50% of MRC-5 cell lines (human lung fibroblast cell lines, as a neutral control); e ERα downregulation measured in MCF-7 cell lines; f Progesteron receptor was measured as a biomarker for ERα antagonism in MCF-7 cell lines; g Concentration that prevents the growth of 50% of Ishikawa cell lines; h Results are presented as mean value ± standard deviation; i 17β-estradiol; j 4-hydroxytamoxifen; k Raloxifene; l 0.9%NaCl; m Not available. * p < 0.05 when compared with control group. ‡ p < 0.05 when compared with 4-OTH; § p < 0.05 when compared with Ral.