Discovery of novel SERMs with a ferrocenyl entity based on the oxabicyclo[2.2.1]heptene scaffold and evaluation of their antiproliferative effects in breast cancer cells

Abstract

We have synthesized a series of novel SERMs bearing a ferrocenyl unit based on a three-dimensional oxabicyclo[2.2.1]heptene core scaffold. These compounds displayed high receptor binding affinities as well as ERα or ERβ selectivity. In cell proliferation assays, we found that these ligands were cytotoxic at micromolar concentrations in both ER-positive and ER-negative breast cancer cells. On further examination, we found that the antiproliferative effects of compounds 9b, 10h and 11b on MCF-7 cells line does not arise from antiestrogenicity, but rather proceeds through a cytotoxic pathway. Possible mechanisms for the unique activities of these ligands were also investigated by molecular modeling. These new ligands could act as scaffolds for the development of novel anti-breast cancer agents.

Current research on anti-breast cancer synthetic compounds

“…1-p-(Ferrocenylcarbonylamino-phenyl)-1,2-di(phydroxyphenyl)-but-1-ene (145) was synthesized and exhibited a signicant antiproliferative activities against MCF-7 and MDA-MB-231 BC cells with 4.53 mM and 1 mM, respectively (Table 6). 129 Zheng et al, 130 (Table 6) on MCF-7 cells line does not arise from antiestrogenicity, but rather proceeds through a cytotoxic pathway.…”

Recent Advancements in the Development of Anti-Breast Cancer Synthetic Small Molecules

“…Moreover, the Selective Estrogen Receptor Modulators (SERMs) bearing a ferrocenyl-oxabicyclo[2.2.1]heptenes were prepared and screened as anti-breast cancer agents. The results exhibited that compounds 144 (IC50 = 3.1 ± 0.5 μM for MCF-7) and 145 (IC50 = 7.8 ± 0.6 μM for MDA-MB-231) (Figure 20) were the most potent anti-proliferative agents against MCF-7 and MDA-MB-231 cancer cell lines [124]. Marinero and coworkers synthesized new derivatives of ferrocenyl compounds and evaluated their anticancer activity against TNBC MDA-MB-231 and MCF-7 cell lines.…”

“…Moreover, the Selective Estrogen Receptor Modulators (SERMs) bearing a ferrocenyl-oxabicyclo[2.2.1]heptenes were prepared and screened as anti-breast cancer agents. The results exhibited that compounds 144 (IC 50 = 3.1 ± 0.5 µM for MCF-7) and 145 (IC 50 = 7.8 ± 0.6 µM for MDA-MB-231) (Figure20) were the most potent antiproliferative agents against MCF-7 and MDA-MB-231 cancer cell lines[124].Marinero and coworkers synthesized new derivatives of ferrocenyl compounds and evaluated their anticancer activity against TNBC MDA-MB-231 and MCF-7 cell lines. All these compounds displayed high antitumor activity with IC 50 values ranging between 0.5 and 4.12 µM.…”

Unexpected reactions of Grignard reagents with selected β-carboalkoxy substituted sulfinate esters

“…[23][24][25][26] DielsAlder chemistry with sulfonate substituents 23 has been extended to the preparation of a variety of structures 24 and has proved particularly useful in the pursuit of the pamamycin macrodiolides 24,27 and estrogen receptor ligands possessing the oxabicyclo[2.2.1]heptene framework. [28][29][30][31] Diels-Alder reactions with sulfinate ester-bearing dienophiles have also been studied. [32][33][34][35] The sulfinate is particularly appealing for its ability to be readily adapted by reduction, 34,36,37 oxidation, [38][39][40] and transformation to sulfoxide.…”