Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Dec;397(12):10091-10107.
doi: 10.1007/s00210-024-03255-9. Epub 2024 Jul 9.

Synthesis, cytotoxicity, anti-inflammatory, anti-metastatic and anti-oxidant activities of novel chalcones incorporating 2-phenoxy-N-arylacetamide and thiophene moieties: induction of apoptosis in MCF7 and HEP2 cells

Nada S Ibrahim  1 , Hager Ahmed Sayed  1 , Marwa Sharaky  2 , Hadeer M Diab  3 , Ahmed H M Elwahy  4 , Ismail A Abdelhamid  5
Affiliations

Synthesis, cytotoxicity, anti-inflammatory, anti-metastatic and anti-oxidant activities of novel chalcones incorporating 2-phenoxy-N-arylacetamide and thiophene moieties: induction of apoptosis in MCF7 and HEP2 cells

Nada S Ibrahim et al. Naunyn Schmiedebergs Arch Pharmacol. 2024 Dec.

Abstract

Eight Novel chalcones were synthesized and their structures were confirmed by different spectral tools. All the prepared compounds were subjected to SRB cytotoxic screening against several cancer cell lines. Compound 5c exerted the most promising effect against MCF7 and HEP2 cells with IC50 values of 9.5 and 12 µg/mL, respectively. Real-time PCR demonstrated the inhibitory effect of compound 5c on the expression level of Antigen kiel 67 (KI-67), Survivin, Interleukin-1beta (IL-1B), Interleukin-6 (IL-6), Cyclooxygenase-2 (COX-2) and Protein kinase B (AKT1) genes. Flow-cytometric analysis of the cell cycle indicated that compound 5c stopped the cell cycle at the G0/G1 and G2/M phases in MCF7 and HEP2 treated cells, respectively. ELISA assay showed that Caspase 8, Caspase 9, P53, BAX, and Glutathione (GSH) were extremely activated and Matrix metalloproteinase 2 (MMP2), Matrix metalloproteinase 9 (MMP9), BCL2, Malondialdehyde (MDA), and IL-6 were deactivated in 5c treated MCF7 and HEP2 cells. Wound healing revealed that chalcone 5c reduced the ability to close the scrape wound and decreased the number of migrating MCF7 and HEP2 cells compared to the untreated cells after 48 h. Theoretical molecular modeling against P53 cancer mutant Y220C and Bcl2 showed binding energies of -22.8 and -24.2 Kcal/mole, respectively, which confirmed our ELISA results.

Keywords: Anti-inflammatory; Anti-oxidant; Chalcones; Intrinsic and extrinsic apoptosis; Wound healing.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics approval: Not applicable. Consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Chemical structures of some naturally occurring chalcones and marketed drug containing thiophene nucleus
Scheme 1
Scheme 1
Design strategy of the synthesized compounds
Scheme 2
Scheme 2
Synthesis of 2-(4-(3-oxo-3-(thiophen-2-yl)prop-1-en-1-yl)phenoxy)-N-arylacetamides 5a–d
Scheme 3
Scheme 3
Synthesis of N-aryl-2-(4-(3-(thiophen-2-yl)acryloyl)phenoxy)acetamides 9a–d
Fig. 2
Fig. 2
Impact of 5c and 9a on the viability of MCF7 and HEP2 cells using SRB assay. GraphPad Prism, version 5, was used to create graphs and analyze the data. The results are expressed as the mean ± SD of 3 separate experiments performed in 5 replicates
Fig. 3
Fig. 3
Distribution of cells in different phases of the cell cycle after the treatment of MCF7 and HEP2 cells with the IC50 value of 5c relative to the untreated control cells
Fig. 4
Fig. 4
Evaluation of migration capacity using a wound‑healing assay following compound 5c treatment for 48 h in MCF7 and HEP2 cells
Fig. 5
Fig. 5
Two-dimensional and three-dimensional mode of interaction of compound 5c with the active site of a) P53 cancer mutant Y220C; b) Bcl2
Fig. 6
Fig. 6
Two-dimensional and three-dimensional mode of interaction of the standard ligands with the active site of a) P53 cancer mutant Y220C; b) Bcl2
See this image and copyright information in PMC

References

    1. Aarreberg LD, Esser-Nobis K, Driscoll C, Shuvarikov A, Roby JA, Gale M (2019) Interleukin-1β induces mtdna release to activate innate immune signaling via cGAS-STING. Mol Cell 74:1–22. 10.1016/j.molcel.2019.02.038 - PMC - PubMed
    1. Abdelwahab RE, Darweesh AF, Ragheb MA, Abdelhamid IA, Elwahy AHM (2023) Synthesis of New 2-(4-(1,4-Dihydropyridin-4-yl)Phenoxy)- N -Arylacetamides and Their Heterocyclic-Fused Derivatives via Hantzsch-Like Reaction. Polycycl Aromat Compd 43:1974–1986. 10.1080/10406638.2022.2039240
    1. Abdelwahab RE, Ragheb MA, Elwahy AHM, Abdelhamid IA, Abdelmoniem AM (2024) Conjugate and regiochemical addition of aminoazoles to 2-(4-(2,2-dicyanovinyl)phenoxy)-N-arylacetamide affording fused pyrimidines linked to phenoxy-N-arylacetamide: antibacterial activity, molecular docking, and DNA binding studies. J Mol Struct 1307:137946. 10.1016/j.molstruc.2024.137946
    1. Abdullah AH, Ibrahim NS, Algethami FK, Elwahy AHM, Abdelhamid IA, Salem ME (2024) Synthesis, molecular docking, and antimicrobial activity of novel scaffolds based on bis(thiazole) linked to 2-phenoxy-N-arylacetamide as new hybrid molecules. J Mol Struct 1302:137506. 10.1016/j.molstruc.2024.137506
    1. Abdullah AH (2023) Ph.D. thesis, Cairo University, Faculty of Science, Department of Chemistry: Synthesis of bis(functional) compounds

Publication types

MeSH terms