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

• Published in: Molecules (Basel, Switzerland) Switzerland), 2024-06, Vol.29 (11), p.2641
• Main Authors: Liu, Chi, Liu, Xinyue, Ma, Qing, Su, Fengyan, Cai, Enbo
• Format: Article
• Language: English
• Subjects: Amino acids; Amino Acids - chemistry; Amino Acids - pharmacology; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; antitumor; Apoptosis; Apoptosis - drug effects; Autophagy - drug effects; Cancer therapies; Cell adhesion & migration; Cell cycle; Cell growth; Cell Proliferation - drug effects; Cervical cancer; Chalcones - chemical synthesis; Chalcones - chemistry; Chalcones - pharmacology; Chemotherapy; Chinese medicine; Cloning; Cytotoxicity; Drug Design; Esters - chemical synthesis; Esters - chemistry; Esters - pharmacology; Ethylenediaminetetraacetic acid; Health aspects; HeLa Cells; Humans; isoliquiritigenin derivatives; Molecular Structure; Phosphatidylinositol 3-Kinases - metabolism; PI3K/Akt/mTOR signaling pathway; Proto-Oncogene Proteins c-akt - metabolism; Radiation; Signal Transduction - drug effects; Structure-Activity Relationship; TOR Serine-Threonine Kinases - metabolism; Toxicity
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules29112641

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 H NMR and C NMR. Among them, compound (IC = 14.36 μM) had a better inhibitory effect on human cervical cancer (Hela) than ISL (IC = 126.5 μM), and it was superior to the positive drug 5-FU (IC = 33.59 μM). The mechanism of the action experiment showed that compound could induce Hela cell apoptosis and autophagy through the PI3K/Akt/mTOR pathway.