Pharmacological explorations of eco-friendly amide substituted (Z)-β-enaminones as anti-breast cancer drugs

Abstract

Amide substituted (Z)-β-enaminones were synthesized by green chemistry and stereospecific synthetic pathway as novel phosphoinositide 3-kinase (PI3K) inhibitors and breast cancer drugs. PI3K inhibition was measured by competitive ELISA. A panel of cancer cell lines including MCF-7 (breast cancer), G-361 (skin cancer), and HCT 116 (colon cancer) were used to assess the anticancer potentials. In the PI3K assay, 2c and 2f were indolent for the proposed inhibitory action, which was recognized from the obtained IC 50 (>1.0 μM). Excellent activity potential of 2a, 2b, and 2d was recognized from the IC 50 range (<0.05 μM) whereas an intermediate action potential was observed for compounds 2e and 2i (IC 50 0.1 and 0.25, respectively). The docking results exclusively proposed that the hydrophobic interactions in the PI3K binding pocket were overwhelmed by the binding affinity of the most potent ligands (2a, 2b, and 2d: inhibitory constant K i = 18.16, 84.87, and 56.14 nM). MTT assay results revealed the antiproliferative activity domination of selected compounds (2a, 2b, and 2d) toward MCF-7. The relative activities of 2a, 2b, and 2d of 84.56, 80.87, and 90.12%, respectively, were comparable to that of the standard, doxorubicin (82.16%). SAR studies demonstrated amide substituted (Z)-β-enaminones as precise PI3K inhibitors to treat breast cancer. K E Y W O R D S amide substituted (Z)-β-enaminones, anticancer, breast cancer, molecular docking, phosphoinositide 3-kinase, SAR

N‐Propargylic β‐enaminones in breast cancer cells: Cytotoxicity, apoptosis, and cell cycle analyses

“…The most cytotoxic NPEs were NPE4, NPE9, NPE16, NPE21, and NPE23 for both breast cancer cells, which have cytotoxic effects similar to the reference drug cisplatin. In the literature, Subramamiam et al [ 9 ] assessed the activity of substituted (Z)‐β‐enaminones on various cancer cells including breast, skin, and colon; however, enaminones were highly effective on MCF‐7 breast cancer cells with the anticancer activity of 78%–90%. In our study, however, all NPEs showed high cytotoxicity with similar IC50s in both breast cancer cells, regardless of cancer type.…”

“…[ 5 ] Designing enaminone derivatives also led to potent anticancer agents. [ 9,10 ] However, the number of studies investigating the anticancer activities of N‐propargylic β‐enaminones (NPEs), which are precursors to such different drug groups, is limited. Herein we investigated the potential cytotoxic and apoptotic effects of 23 different NPEs on human breast cancer cells (MDA‐MB‐231 and MCF‐7) and human embryonic kidney cells (HEK‐293).…”

TRAF2 and NCK-Interacting Kinase Inhibitors for Colorectal Cancer: In Vitro and Theoretical Validations

“…Subsequently, the target compound LC_112060 and Doxorubicin (standard) were dissolved in DMSO at a concentration of 10–100 (μg/mL). These concentrations were treated up to 48 h and then 10 μL of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) (10 mg/mL in a PBS buffer)) was added to it and it was again incubated for 6 to 8 h at 37 °C. , Further, formazan crystals that were formed during the process were dissolved in 100 μL of DMSO, after removing the DMEM, from corresponding plates. The optical density (OD) was resolute at 540 nm in the BioRad ELISA plate reader.…”

Exploration of anti-breast cancer effects of Terminalia chebula extract on DMBA-induced mammary carcinoma in Sprague Dawley rats

“…The name MCF-7 cell lines are the official name and its Research Resource Identifier (RRID) is Cellosaurus MCF-7 (CVCL_0031). MCF-7 cells obtained were preserved and maintained in DMEM medium supplemented with 10% fetal bovine serum, streptomycin (100 μg/ml), and penicillin (100 U/ml) [43][44][45]. The cells were further incubated at 37°C in a humidified (5% CO 2 ) atmosphere.…”