Novel SERMs based on 3-aryl-4-aryloxy-2H-chromen-2-one skeleton - A possible way to dual ERα/VEGFR-2 ligands for treatment of breast cancer

Antiangiogenic Effects of Coumarins against Cancer: From Chemistry to Medicine

“…These results showed a significant decrease in the VEGF-triggered phosphorylated forms of ERK1/2 and Akt, which was corroborated by in vivo observations on chick chorioallantoic membrane [138]. Luo and co-workers also showed that 3-aryl-4-anilino/aryloxy-2 H -chromen-2-one analogues significantly affected breast cancer through the inhibition of estrogen receptor-α and VEGFR-2 [139]. In another study, coumarin-conjugated benzophenone analogs showed promising antitumor activity against Ehrlich ascites carcinoma and Dalton’s lymphoma ascites cell lines.…”

New piperidine derivative DTPEP acts as dual‐acting anti‐breast cancer agent by targeting ERα and downregulating PI3K/Akt‐PKCα leading to caspase‐dependent apoptosis

“…Some report suggests activity of tamoxifen against ER‐negative breast cancer, possibly through some ER‐independent off‐target effect . Some groups have attempted collective targeting of ER and other targets in breast cancer, mostly through hybrid molecules . In pursuit of new drug discovery, a series of constrained tricyclic compounds of substituted dibenzo[b,f]thiepine and dibenzo[b,f]oxepines that were structurally analogous to tamoxifen were synthesized.…”

3-Phenylcoumarins as a Privileged Scaffold in Medicinal Chemistry: The Landmarks of the Past Decade

“…A series of 18 4-anilino derivatives has been designed to obtain novel selective ERα modulators, and their antiproliferative activity has been evaluated against MCF-7 and Ishikawa cell lines, showing, for most of the derivatives, higher activity than tamoxifen, with the best being compound 57, with an IC 50 value of 4.52 µM [140]. In a 4-anilino/aryloxy comparison, compound 58 has been the most interesting molecule of the series as a dual ERα selective antagonist modulator/VEGFR-2 inhibitor [141]. The ERα binding affinity (IC 50 = 2.19 mM) occurs via suppressing the expression of progesterone receptor (PgR) mRNA in MCF-7 cells, and, in the same cells, may inhibit the activation of VEGFR-2 and subsequent signaling transduction of the Raf-1/MAPK/ERK pathway [141].…”

“…In a 4-anilino/aryloxy comparison, compound 58 has been the most interesting molecule of the series as a dual ERα selective antagonist modulator/VEGFR-2 inhibitor [141]. The ERα binding affinity (IC 50 = 2.19 mM) occurs via suppressing the expression of progesterone receptor (PgR) mRNA in MCF-7 cells, and, in the same cells, may inhibit the activation of VEGFR-2 and subsequent signaling transduction of the Raf-1/MAPK/ERK pathway [141]. Compounds with similar substitutions at position 4, but with variability at position 3 of the coumarin scaffold, have been evaluated in vitro against MCF-7, HepG2, HCT-116 and human pancreatic carcinoma (Panc-1) cell lines by the same authors, displaying antiproliferative activities comparable to fluouracil.…”