Antitumor activity and transcriptome sequencing (RNA-seq) analyses of hepatocellular carcinoma cells in response to exposure triterpene-nucleoside conjugates

• Published in: European journal of medicinal chemistry 2024-10, Vol.276, p.116635, Article 116635
• Main Authors: Wang, Qiang, Ma, Fangchao, Wang, Jingchen, Xu, Hongde, Li, Keyan, Cheng, Yung-Yi, Chen, Xiqiang, Qu, Shuhao, Wei, Tingting, Hao, Xiaofei, Kong, Mingyue, Xie, Chengping, Wang, Wei, Wang, Yanli, Jeong, Lak Shin
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antitumor activity; Apoptosis - drug effects; autophagy; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - pathology; Cell Line, Tumor; Cell Proliferation - drug effects; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Hepatocellular carcinoma cells; Humans; Liver Neoplasms - drug therapy; Liver Neoplasms - pathology; Mice; Mice, Nude; Molecular Structure; Nucleosides; Nucleosides - chemical synthesis; Nucleosides - chemistry; Nucleosides - pharmacology; Pentacyclic triterpene; Structure-Activity Relationship; Transcriptome - drug effects; Transcriptome sequencing analyses; Triterpenes - chemical synthesis; Triterpenes - chemistry; Triterpenes - pharmacology; Zebrafish
• ISSN: 0223-5234; 1768-3254; 1768-3254
• DOI: 10.1016/j.ejmech.2024.116635

Fifteen betulonic/betulinic acid conjugated with nucleoside derivatives were synthesized to enhance antitumor potency and water solubility. Among these, the methylated betulonic acid-azidothymidine compound (8c) exhibited a broad-spectrum of antitumor activity against three tested tumor cell lines, including SMMC-7721 (IC50 = 5.02 μM), KYSE-150 (IC50 = 5.68 μM), and SW620 (IC50 = 4.61 μM) and along with lower toxicity (TC50 > 100 μM) estimated by zebrafish embryos assay. Compared to betulinic acid (