Synthesis and In Vitro Photocytotoxicity of 9-/13-Lipophilic Substituted Berberine Derivatives as Potential Anticancer Agents. 2020

Hong-Jhih Lin, and Jinn-Hsuan Ho, and Li-Chen Tsai, and Fang-Yu Yang, and Ling-Ling Yang, and Cheng-Deng Kuo, and Lih-Geeng Chen, and Yi-Wen Liu, and Jin-Yi Wu
Department of Microbiology, Immunology and Biopharmaceuticals, College of Life Sciences, National Chiayi University, Chiayi 60004, Taiwan.

The objective of this study was to synthesize the 9-/13-position substituted berberine derivatives and evaluate their cytotoxic and photocytotoxic effects against three human cancer cell lines. Among all the synthesized compounds, 9-O-dodecyl- (5e), 13-dodecyl- (6e), and 13-O-dodecyl-berberine (7e) exhibited stronger growth inhibition against three human cancer cell lines, (HepG2, HT-29 and BFTC905), in comparison with structurally related berberine (1). These three compounds also showed the photocytotoxicity in human cancer cells in a concentration-dependent and light dose-dependent manner. Through flow cytometry analysis, we found out a lipophilic group at the 9-/13-position of berberine may have facilitated its penetration into test cells and hence enhanced its photocytotoxicity on the human liver cancer cell HepG2. Further, in cell cycle analysis, 5e, 6e, and 7e induced HepG2 cells to arrest at the S phase and caused apoptosis upon irradiation. In addition, photodynamic treatment of berberine derivatives 5e, 6e, and 7e again showed a significant photocytotoxic effects on HepG2 cells, induced remarkable cell apoptosis, greatly increased intracellular ROS level, and the loss of mitochondrial membrane potential. These results over and again confirmed that berberine derivatives 5e, 6e, and 7e greatly enhanced photocytotoxicity. Taken together, the test data led us to conclude that berberine derivatives with a dodecyl group at the 9-/13-position could be great candidates for the anti-liver cancer medicines developments.

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
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
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
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
D001599 Berberine An alkaloid from Hydrastis canadensis L., Berberidaceae. It is also found in many other plants. It is relatively toxic parenterally, but has been used orally for various parasitic and fungal infections and as antidiarrheal. Umbellatine
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
D017382 Reactive Oxygen Species Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of SIGNAL TRANSDUCTION and GENE EXPRESSION, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS. Active Oxygen Species,Oxygen Radical,Oxygen Radicals,Pro-Oxidant,Reactive Oxygen Intermediates,Active Oxygen,Oxygen Species, Reactive,Pro-Oxidants,Oxygen, Active,Pro Oxidant,Pro Oxidants,Radical, Oxygen
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
D049109 Cell Proliferation All of the processes involved in increasing CELL NUMBER including CELL DIVISION. Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular

Related Publications

Hong-Jhih Lin, and Jinn-Hsuan Ho, and Li-Chen Tsai, and Fang-Yu Yang, and Ling-Ling Yang, and Cheng-Deng Kuo, and Lih-Geeng Chen, and Yi-Wen Liu, and Jin-Yi Wu
April 2011, European journal of medicinal chemistry,
Hong-Jhih Lin, and Jinn-Hsuan Ho, and Li-Chen Tsai, and Fang-Yu Yang, and Ling-Ling Yang, and Cheng-Deng Kuo, and Lih-Geeng Chen, and Yi-Wen Liu, and Jin-Yi Wu
August 2006, Bioorganic & medicinal chemistry letters,
Hong-Jhih Lin, and Jinn-Hsuan Ho, and Li-Chen Tsai, and Fang-Yu Yang, and Ling-Ling Yang, and Cheng-Deng Kuo, and Lih-Geeng Chen, and Yi-Wen Liu, and Jin-Yi Wu
October 2016, Bioorganic & medicinal chemistry letters,
Hong-Jhih Lin, and Jinn-Hsuan Ho, and Li-Chen Tsai, and Fang-Yu Yang, and Ling-Ling Yang, and Cheng-Deng Kuo, and Lih-Geeng Chen, and Yi-Wen Liu, and Jin-Yi Wu
August 2016, Bioorganic & medicinal chemistry letters,
Hong-Jhih Lin, and Jinn-Hsuan Ho, and Li-Chen Tsai, and Fang-Yu Yang, and Ling-Ling Yang, and Cheng-Deng Kuo, and Lih-Geeng Chen, and Yi-Wen Liu, and Jin-Yi Wu
May 2019, International journal of molecular sciences,
Hong-Jhih Lin, and Jinn-Hsuan Ho, and Li-Chen Tsai, and Fang-Yu Yang, and Ling-Ling Yang, and Cheng-Deng Kuo, and Lih-Geeng Chen, and Yi-Wen Liu, and Jin-Yi Wu
January 2013, Bioorganic & medicinal chemistry letters,
Hong-Jhih Lin, and Jinn-Hsuan Ho, and Li-Chen Tsai, and Fang-Yu Yang, and Ling-Ling Yang, and Cheng-Deng Kuo, and Lih-Geeng Chen, and Yi-Wen Liu, and Jin-Yi Wu
January 2018, Anti-cancer agents in medicinal chemistry,
Hong-Jhih Lin, and Jinn-Hsuan Ho, and Li-Chen Tsai, and Fang-Yu Yang, and Ling-Ling Yang, and Cheng-Deng Kuo, and Lih-Geeng Chen, and Yi-Wen Liu, and Jin-Yi Wu
July 2007, Journal of medicinal chemistry,
Hong-Jhih Lin, and Jinn-Hsuan Ho, and Li-Chen Tsai, and Fang-Yu Yang, and Ling-Ling Yang, and Cheng-Deng Kuo, and Lih-Geeng Chen, and Yi-Wen Liu, and Jin-Yi Wu
July 2012, Bioorganic & medicinal chemistry,
Hong-Jhih Lin, and Jinn-Hsuan Ho, and Li-Chen Tsai, and Fang-Yu Yang, and Ling-Ling Yang, and Cheng-Deng Kuo, and Lih-Geeng Chen, and Yi-Wen Liu, and Jin-Yi Wu
August 2006, Bioorganic & medicinal chemistry letters,
Copied contents to your clipboard!