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

• Published in: Molecules (Basel, Switzerland) Vol. 25; no. 5; p. 1162
• Main Authors: Wu, Lintao, Yang, Yuting, Wang, Zhijun, Wu, Xi, Su, Feng, Li, Mengyao, Jing, Xiaobi, Han, Chun
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 05.03.2020; MDPI
• Subjects: 5-Fluorouracil; Amides - chemistry; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; antiproliferative activities; Antitumor activity; Apoptosis; aromatic amide-substituted; Aromatic compounds; Benzimidazoles; Benzimidazoles - chemistry; Cancer; Cell adhesion & migration; Cell cycle; Cell Cycle - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; chalcones; Chalcones - chemical synthesis; Chalcones - chemistry; Chalcones - pharmacology; Chemistry Techniques, Synthetic; Dose-Response Relationship, Drug; Drug Design; Drug dosages; Gene Expression Regulation, Neoplastic; Humans; MDM2 protein; Medical research; Molecular Structure; Mutants; Mutation; NMR; Nuclear magnetic resonance; p53 Protein; Protein expression; Proteins; Structure-Activity Relationship; tp53 protein; Tumor cell lines; Tumor cells; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Tumors; upregulating; Germany; aromatic amide-substituted; chalcones; upregulating; antiproliferative activities; TP53 protein
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules25051162

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 , , , , , 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 ( ) cells. A preliminary mechanistic study suggested that these compounds act by upregulating the expression of protein in tumor cells without inhibiting the MDM2- interaction.