AUTHOR=Jiang Taibai , Xie Guangtong , Zeng Zhirui , Lan Junjie , Liu Hanfei , Li Jinyu , Ren Hai , Chen Tengxiang , Pan Weidong 

TITLE=A novel class of C14-sulfonate-tetrandrine derivatives as potential chemotherapeutic agents for hepatocellular carcinoma

JOURNAL=Frontiers in Chemistry

VOLUME=10

YEAR=2023

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2022.1107824

DOI=10.3389/fchem.2022.1107824

ISSN=2296-2646

ABSTRACT=<p>Hepatocellular carcinoma (HCC), the most common malignancy of the liver, exhibits high recurrence and metastasis. Structural modifications of natural products are crucial resources of antitumor drugs. This study aimed to synthesize C-14 derivatives of tetrandrine and evaluate their effects on HCC. Forty C-14 sulfonate tetrandrine derivatives were synthesized and their <italic>in vitro</italic> antiproliferative was evaluated against four hepatoma (HepG-2, SMMC-7721, QGY-7701, and SK-Hep-1) cell lines. For all tested cells, most of the modified compounds were more active than the lead compound, tetrandrine. In particular, 14-O-(5-chlorothiophene-2-sulfonyl)-tetrandrine (<bold>33</bold>) exhibited the strongest antiproliferative effect, with half-maximal inhibitory concentration values of <bold>1.65</bold>, <bold>2.89</bold>, <bold>1.77</bold>, and <bold>2.41</bold> μM for the four hepatoma cell lines, respectively. Moreover, <bold>33</bold> was found to induce apoptosis <italic>via</italic> a mitochondria-mediated intrinsic pathway <italic>via</italic> flow cytometry and western blotting analysis. In addition, colony formation, wound healing, and transwell assays demonstrated that <bold>33</bold> significantly inhibited HepG-2 and SMMC-7721 cell proliferation, migration, and invasion, indicating that it might potentially be a candidate for an anti-HCC therapy in the future.</p>