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. 2024 Jun 3;29(11):2641.
doi: 10.3390/molecules29112641.

Design, Synthesis, and Antitumor Activity of Isoliquiritigenin Amino Acid Ester Derivatives

Chi Liu  1 , Xinyue Liu  1 , Qing Ma  1 , Fengyan Su  1 , Enbo Cai  1
Affiliations

Design, Synthesis, and Antitumor Activity of Isoliquiritigenin Amino Acid Ester Derivatives

Chi Liu et al. Molecules. .

Abstract

Isoliquiritigenin (ISL) is a chalcone that has shown great potential in the treatment of cancer. However, its relatively weak activity and low water solubility limit its clinical application. In this study, we designed and synthesized 21 amino acid ester derivatives of ISL and characterized the compounds using 1H NMR and 13C NMR. Among them, compound 9 (IC50 = 14.36 μM) had a better inhibitory effect on human cervical cancer (Hela) than ISL (IC50 = 126.5 μM), and it was superior to the positive drug 5-FU (IC50 = 33.59 μM). The mechanism of the action experiment showed that compound 9 could induce Hela cell apoptosis and autophagy through the PI3K/Akt/mTOR pathway.

Keywords: PI3K/Akt/mTOR signaling pathway; antitumor; cervical cancer; isoliquiritigenin derivatives.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Scheme 1
Scheme 1
Synthetic route of target compounds 1–23.
Figure 1
Figure 1
(A) ISL inhibits the migration of Hela cells under microscopy image of the degree of healing of cell scratches. (B) Compound 9 inhibits the migration of Hela cells under microscopy image of the degree of healing of cell scratches. (C) Scratch healing rate compared to the control group, ** p < 0.01.
Figure 2
Figure 2
ISL and compound 9 inhibit the proliferation of Hela cells.
Figure 3
Figure 3
DAPI staining was used to detect the effects of ISL and compound 9 on the morphology of Hela cells.
Figure 4
Figure 4
Annexin V-FITC/PI double-staining assay was used to investigate the effect of compound 9 on the apoptosis of Hela cells; compared to the control group, * p < 0.05, ** p < 0.01.
Figure 4
Figure 4
Annexin V-FITC/PI double-staining assay was used to investigate the effect of compound 9 on the apoptosis of Hela cells; compared to the control group, * p < 0.05, ** p < 0.01.
Figure 5
Figure 5
(A) Three-dimensional map of ISL-PI3K protein. (B) Three-dimensional map of compound 9-PI3K protein. (C) Three-dimensional map of ISL-mTOR protein. (D) Three-dimensional map of compound 9-mTOR protein.
Figure 5
Figure 5
(A) Three-dimensional map of ISL-PI3K protein. (B) Three-dimensional map of compound 9-PI3K protein. (C) Three-dimensional map of ISL-mTOR protein. (D) Three-dimensional map of compound 9-mTOR protein.
Figure 6
Figure 6
Effects of ISL and compound 9 on mRNA expression in Hela cells; compared to the control group, * p < 0.05, ** p < 0.01.
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