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
. 2020 Mar 5;25(5):1162.
doi: 10.3390/molecules25051162.

Design, Synthesis, and Biological Evaluation of Aromatic Amide-Substituted Benzimidazole-Derived Chalcones. The Effect of Upregulating TP53 Protein Expression

Lintao Wu  1 , Yuting Yang  2 , Zhijun Wang  1 , Xi Wu  1 , Feng Su  1 , Mengyao Li  1 , Xiaobi Jing  3 , Chun Han  1
Affiliations

Design, Synthesis, and Biological Evaluation of Aromatic Amide-Substituted Benzimidazole-Derived Chalcones. The Effect of Upregulating TP53 Protein Expression

Lintao Wu et al. Molecules. .

Abstract

A series of benzimidazole-derived chalcones containing aromatic amide substituent were designed and synthesized. All of the chalcone compounds were tested for their in vitro antitumor activity against human cancer cell lines (HCT116, HepG2, A549, and CRL-5908). The antiproliferative activity of compounds 3, 6, 9, 14, 15, 16 against HCT116 cells was significantly better than that that of 5-Fluorouracil (IC50: 94.63 µM). The antitumor activity of these compounds showed obvious differences between the wild type HCT116 and mutant HCT116 (TP53-/-) cells. A preliminary mechanistic study suggested that these compounds act by upregulating the expression of TP53 protein in tumor cells without inhibiting the MDM2-TP53 interaction.

Keywords: TP53 protein; antiproliferative activities; aromatic amide-substituted; chalcones; upregulating.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1
Reagents and conditions: (a) lactic acid, 4 M HCl, reflux; (b) CrO3, acetic acid, 90–105 °C (c) terephthalaldehydic acid, 10% NaOH aqueous, ethanol, rt; (d) SOCl2, DMF, reflux; (e) K2CO3, DMF, Aromatic amine, 0–5 °C.
Figure 1
Figure 1
G2/M phase arrest and the induction of apoptosis in HCT116 cells after treatment with compounds 6, 9, and Nutlin-3a.
Figure 2
Figure 2
The activation of p53 pathway and p53 up regulation in HCT116 cells by compounds 6, 9 (western blotting).
See this image and copyright information in PMC

References

    1. Duffy M.J. The war on cancer: Are we winning? Tumor Biol. 2013;34:1275–1284. doi: 10.1007/s13277-013-0759-2. - DOI - PubMed
    1. Hanahan D., Weinberg R.A. Hallmarks of cancer: The next generation. Cell. 2011;144:646–674. doi: 10.1016/j.cell.2011.02.013. - DOI - PubMed
    1. Khoo K.H., Verma C.S., Lane D.P. Drugging the p53 pathway: Understanding the route to clinical efficacy. Nat. Rev. Drug Discov. 2014;13:217–236. doi: 10.1038/nrd4236. - DOI - PubMed
    1. Xie X., Wang X., Liao W., Fei R., Wu N., Cong X., Chen Q., Wei L., Wang Y., Chen H. MYL6B, a myosin light chain, promotes MDM2-mediated p53 degradation and drives HCC development. J. Exp. Clin. Cancer Res. 2018;37:28. doi: 10.1186/s13046-018-0693-7. - DOI - PMC - PubMed
    1. Brown C.J., Lain S., Verma C.S., Fersht A.R., Lane D.P. Awakening guardian angels: Drugging the p53 pathway. Nat. Rev. Cancer. 2009;9:862–873. doi: 10.1038/nrc2763. - DOI - PubMed

MeSH terms