Design, synthesis, and biological evaluation of chalcones for anticancer properties targeting glycogen synthase kinase 3 beta

Abstract

Chalcones compounds have been investigated to exhibit anticancer activity through various physiological modes of action. In order to develop chalcone compounds with novel anticancer-related modes of action, diverse chalcone compounds were designed and synthesized. Variously substituted poly-methoxy chalcone compounds 1–17 were prepared, and their structures were identified using high-resolution mass spectrometry (HR/MS) and nuclear magnetic resonance (NMR) experiments. Long-term survival clonogenic assay was applied to evaluate their anti-cancer abilities and revealed that their GI50 values ranged between 1.33 and 172.20 μM. When MCF-7SC cells were treated with various concentrations of compound 14, reduced cell viability and induced apoptosis in MCF-7SC cells were observed in a dose-dependent manner. Wound healing assay demonstrated that compound 14 prevented the MCF7-SC migrated cells at non-lethal concentrations after 12 and 24 h of exposure. The efficiency of compound 14 on the levels of Epithelial-mesenchymal transition (EMT) markers was accessed by the western blot analysis. For the concrete understanding of anticancer properties at the molecular level, in vitro kinase assays on 12 cancer related proteins were carried out. Glycogen synthase kinase 3 beta (GSK3β) was most effectively inhibited by compound 14 with 89% inhibitory activity at 10 µM against GSK3β. The binding mode of compound 14 with GSK3β was reinforced through in silico experiments, which demonstrated compound 14 binds with GSK3β at binding affinity ranged between − 7.5 kcal/mol and − 6.8 kcal/mol. SwissADME analysis provided the druggability and leadlikeness of compound 14, which unveiled drug development possibilities of chalcone compound 14.

Resveratrol-loaded gold nanoparticles enhance caspase-mediated apoptosis in PANC-1 pancreatic cells via mitochondrial intrinsic apoptotic pathway

“…Cells that receive apoptotic signals activated p53 phosphorylation to promote apoptosis with tight control (Haupt et al 2003). PARP, which is located in the cell nucleus and involved in DNA repair, was another key factor in apoptosis (Ahn et al 2022). In programmed cell death, PARP induced poly(ADP-ribose) (PAR) production, which stimulated apoptosis inducing factor (AIF) from mitochondria (Ahn et al 2022).…”

“…PARP, which is located in the cell nucleus and involved in DNA repair, was another key factor in apoptosis (Ahn et al 2022). In programmed cell death, PARP induced poly(ADP-ribose) (PAR) production, which stimulated apoptosis inducing factor (AIF) from mitochondria (Ahn et al 2022). All our results of mRNA and protein assays including animal studies represented a higher level of apoptosis in RVT@PVP-GNPs-treated group compared with free RVT, demonstrating its potential as a therapeutic drug for cancer treatment.…”

Design, Synthesis and In Silico Molecular Docking Evaluation of New Series of 1,2,3‐Triazole Derivatives as Potent Antimicrobial Agents

“…The results are provided in parts per million (ppm) down field from the residual CDCl 3 /DMSO-d 6 . Using CDCl 3 and DMSO-d 6 as NMR solvents, 13 C-NMR spectra were captured using a Jeol Eclipse 100-125 MHz spectrometer. A JEOL JMS-600H apparatus was utilised to record mass spectra through the use of an electro spray ionisation (ESI) detector.…”

“…Supporting information includes general experimental details on spectral characterization, biological activity evaluation, computational docking studies, and copies of IR, 1 H NMR, 13 C NMR and HRMS spectra (Figure S1-S43).…”

“…The solid thus obtained was filtered, washed with excess water, and then dried to get the desired pure chalcones with 1,2,3-triazole scaffold 4 a-k. The structures of the synthesized compounds were elucidated by the IR, 1 H NMR and 13 C NMR spectral analysis. The structure of the titled compound 4 a was deduced from IR spectrum, which showed the absorption bands of the À CH and =CH functional groups at 2926.21 cm À 1 , 3205.20 cm À 1 .…”