Development of novel 9-O-substituted-13-octylberberine derivatives as potential anti-hepatocellular carcinoma agents. 2022

Jichao Chen, and Yiping Duan, and Xiaoxuan Yu, and Jiarou Zhong, and Jing Bai, and Nian-Guang Li, and Zheying Zhu, and Jinyi Xu
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.

A series of novel 9-O-substituted-13-octylberberine derivatives were designed, synthesised and evaluated for their anti-hepatocellular carcinoma (HCC) activities. Compound 6k showed the strongest activity against three human hepatoma cells including HepG2, Sk-Hep-1 and Huh-7 cells with IC50 values from 0.62 to 1.69 μM, which were much superior to berberine (IC50 >50 μM). More importantly, 6k exhibited lower cytotoxicity against normal hepatocytes L-02 with good lipid-water partition properties. The mechanism studies revealed that 6k caused G2/M phase arrest of the cell cycle, stabilised G-quadruplex DNA, and induced apoptosis via a mitochondrial apoptotic pathway. Finally, the in vivo anti-HCC activity of 6k was validated in the H22 liver cancer xenograft mouse model. Collectively, the current study would provide a new insight into the discovery of novel, safe and effective anti-HCC agents.

UI MeSH Term Description Entries
D008113 Liver Neoplasms Tumors or cancer of the LIVER. Cancer of Liver,Hepatic Cancer,Liver Cancer,Cancer of the Liver,Cancer, Hepatocellular,Hepatic Neoplasms,Hepatocellular Cancer,Neoplasms, Hepatic,Neoplasms, Liver,Cancer, Hepatic,Cancer, Liver,Cancers, Hepatic,Cancers, Hepatocellular,Cancers, Liver,Hepatic Cancers,Hepatic Neoplasm,Hepatocellular Cancers,Liver Cancers,Liver Neoplasm,Neoplasm, Hepatic,Neoplasm, Liver
D006528 Carcinoma, Hepatocellular A primary malignant neoplasm of epithelial liver cells. It ranges from a well-differentiated tumor with EPITHELIAL CELLS indistinguishable from normal HEPATOCYTES to a poorly differentiated neoplasm. The cells may be uniform or markedly pleomorphic, or form GIANT CELLS. Several classification schemes have been suggested. Hepatocellular Carcinoma,Hepatoma,Liver Cancer, Adult,Liver Cell Carcinoma,Liver Cell Carcinoma, Adult,Adult Liver Cancer,Adult Liver Cancers,Cancer, Adult Liver,Cancers, Adult Liver,Carcinoma, Liver Cell,Carcinomas, Hepatocellular,Carcinomas, Liver Cell,Cell Carcinoma, Liver,Cell Carcinomas, Liver,Hepatocellular Carcinomas,Hepatomas,Liver Cancers, Adult,Liver Cell Carcinomas
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D059447 Cell Cycle Checkpoints Regulatory signaling systems that control the progression through the CELL CYCLE. They ensure that the cell has completed, in the correct order and without mistakes, all the processes required to replicate the GENOME and CYTOPLASM, and divide them equally between two daughter cells. If cells sense they have not completed these processes or that the environment does not have the nutrients and growth hormones in place to proceed, then the cells are restrained (or "arrested") until the processes are completed and growth conditions are suitable. Cell Cycle Arrest,Cell Cycle Control,Cell Cycle Transition Points,Cell Cycle-Transition Points,Arrest, Cell Cycle,Arrests, Cell Cycle,Cell Cycle Arrests,Cell Cycle Checkpoint,Cell Cycle Controls,Cell Cycle-Transition Point,Checkpoint, Cell Cycle,Checkpoints, Cell Cycle,Control, Cell Cycle,Controls, Cell Cycle,Cycle-Transition Point, Cell,Point, Cell Cycle-Transition

Related Publications

Jichao Chen, and Yiping Duan, and Xiaoxuan Yu, and Jiarou Zhong, and Jing Bai, and Nian-Guang Li, and Zheying Zhu, and Jinyi Xu
December 2016, Bioorganic & medicinal chemistry letters,
Jichao Chen, and Yiping Duan, and Xiaoxuan Yu, and Jiarou Zhong, and Jing Bai, and Nian-Guang Li, and Zheying Zhu, and Jinyi Xu
December 2018, Molecules (Basel, Switzerland),
Jichao Chen, and Yiping Duan, and Xiaoxuan Yu, and Jiarou Zhong, and Jing Bai, and Nian-Guang Li, and Zheying Zhu, and Jinyi Xu
February 2020, Molecules (Basel, Switzerland),
Jichao Chen, and Yiping Duan, and Xiaoxuan Yu, and Jiarou Zhong, and Jing Bai, and Nian-Guang Li, and Zheying Zhu, and Jinyi Xu
February 2017, European journal of medicinal chemistry,
Jichao Chen, and Yiping Duan, and Xiaoxuan Yu, and Jiarou Zhong, and Jing Bai, and Nian-Guang Li, and Zheying Zhu, and Jinyi Xu
April 2011, European journal of medicinal chemistry,
Jichao Chen, and Yiping Duan, and Xiaoxuan Yu, and Jiarou Zhong, and Jing Bai, and Nian-Guang Li, and Zheying Zhu, and Jinyi Xu
December 2019, Journal of enzyme inhibition and medicinal chemistry,
Jichao Chen, and Yiping Duan, and Xiaoxuan Yu, and Jiarou Zhong, and Jing Bai, and Nian-Guang Li, and Zheying Zhu, and Jinyi Xu
February 2020, Journal of medicinal chemistry,
Jichao Chen, and Yiping Duan, and Xiaoxuan Yu, and Jiarou Zhong, and Jing Bai, and Nian-Guang Li, and Zheying Zhu, and Jinyi Xu
February 2017, Bioorganic & medicinal chemistry letters,
Jichao Chen, and Yiping Duan, and Xiaoxuan Yu, and Jiarou Zhong, and Jing Bai, and Nian-Guang Li, and Zheying Zhu, and Jinyi Xu
September 2018, European journal of medicinal chemistry,
Jichao Chen, and Yiping Duan, and Xiaoxuan Yu, and Jiarou Zhong, and Jing Bai, and Nian-Guang Li, and Zheying Zhu, and Jinyi Xu
February 2024, ACS chemical neuroscience,
Copied contents to your clipboard!