Synthesis and biological evaluation of N(9)-substituted harmine derivatives as potential anticancer agents. 2016

Hongtao Du, and Shan Tian, and Juncheng Chen, and Hongling Gu, and Na Li, and Junru Wang
Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Science, Northwest A&F University, Yangling 712100, Shaanxi Province, PR China; College of Plant Protection, Northwest A&F University, Yangling 712100, Shaanxi Province, PR China. Electronic address: duht@nwsuaf.edu.cn.

A series of N(9)-substituted harmine derivatives were synthesized and evaluated for their anticancer activity on a panel of cancer cell lines, their apoptosis induction and their cell cycle effects. The results showed that N(9)-substituted harmine derivatives had anticancer effects. In particular, N(9)-haloalkyl derivatives 9a-9c and N(9)-acyl harmine derivatives 11c and 11d, with IC50 values less than 1μM, were more potent than doxorubicin against A-549 and/or MCF-7 cell lines. Moreover, structure-activity relationships (SARs) indicated that introducing a haloalkyl or benzenesulfonyl group in the N(9)-position of harmine could significantly increase the anticancer activity. The most active compound (11d) caused cell cycle arrest in the G2/M phase, and induced cell apoptosis in a dose-dependent manner.

UI MeSH Term Description Entries
D004354 Drug Screening Assays, Antitumor Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals. Anticancer Drug Sensitivity Tests,Antitumor Drug Screens,Cancer Drug Tests,Drug Screening Tests, Tumor-Specific,Dye Exclusion Assays, Antitumor,Anti-Cancer Drug Screens,Antitumor Drug Screening Assays,Tumor-Specific Drug Screening Tests,Anti Cancer Drug Screens,Anti-Cancer Drug Screen,Antitumor Drug Screen,Cancer Drug Test,Drug Screen, Anti-Cancer,Drug Screen, Antitumor,Drug Screening Tests, Tumor Specific,Drug Screens, Anti-Cancer,Drug Screens, Antitumor,Drug Test, Cancer,Drug Tests, Cancer,Screen, Anti-Cancer Drug,Screen, Antitumor Drug,Screens, Anti-Cancer Drug,Screens, Antitumor Drug,Test, Cancer Drug,Tests, Cancer Drug,Tumor Specific Drug Screening Tests
D006247 Harmine Alkaloid isolated from seeds of PEGANUM HARMALA; ZYGOPHYLLACEAE. It is identical to banisterine, or telepathine, from Banisteria caapi and is one of the active ingredients of hallucinogenic drinks made in the western Amazon region from related plants. It has no therapeutic use, but (as banisterine) was hailed as a cure for postencephalitic PARKINSON DISEASE in the 1920's. 9H-Pyrido(3,4-b)indole, 7-methoxy-1-methyl-,Banisterine,Leucoharmine,Telepathine,Yageine
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000072283 A549 Cells An immortalized cell line derived from human ADENOCARCINOMA, ALVEOLAR basal epithelial cells isolated from the lungs of a male patient in 1972. The cell line is positive for KERATIN, can synthesize LECITHIN, and contains high levels of POLYUNSATURATED FATTY ACIDS in its PLASMA MEMBRANE. It is used as a model for PULMONARY ALVEOLI function and virus infections, as a TRANSFECTION host, and for PRECLINICAL DRUG EVALUATION. A549 Cell Line,A549 Cell,A549 Cell Lines,Cell Line, A549,Cell Lines, A549,Cell, A549,Cells, A549
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
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
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
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
D059565 G2 Phase Cell Cycle Checkpoints CELL CYCLE regulatory signaling systems that are triggered by DNA DAMAGE or lack of nutrients during G2 PHASE. When triggered they restrain cells transitioning from G2 phase to M PHASE. Antephase Checkpoint,G2 Cell Cycle Arrest,G2 Cell Cycle Checkpoints,G2 Cell Cycle Control,G2 Phase Checkpoints,G2 Restriction Point,G2-M Cell Cycle Checkpoint,Antephase Checkpoints,Checkpoint, Antephase,Checkpoint, G2 Phase,Checkpoints, Antephase,Checkpoints, G2 Phase,G2 M Cell Cycle Checkpoint,G2 Phase Checkpoint,G2 Restriction Points,Restriction Point, G2,Restriction Points, G2
D059566 M Phase Cell Cycle Checkpoints The cellular signaling system that halts the progression of cells through MITOSIS or MEIOSIS if a defect that will affect CHROMOSOME SEGREGATION is detected. M Phase Cell Cycle Checkpoint,M Phase Cell Cycle Arrest,M Phase Checkpoint,Mitotic Checkpoints,Mitotic Spindle Checkpoints,Spindle Assembly Checkpoint,Spindle Assembly Checkpoint Network,Assembly Checkpoint, Spindle,Assembly Checkpoints, Spindle,Checkpoint, M Phase,Checkpoint, Mitotic,Checkpoint, Mitotic Spindle,Checkpoint, Spindle Assembly,Checkpoints, M Phase,Checkpoints, Mitotic,Checkpoints, Mitotic Spindle,Checkpoints, Spindle Assembly,M Phase Checkpoints,Mitotic Checkpoint,Mitotic Spindle Checkpoint,Phase Checkpoint, M,Spindle Assembly Checkpoints,Spindle Checkpoint, Mitotic,Spindle Checkpoints, Mitotic

Related Publications

Hongtao Du, and Shan Tian, and Juncheng Chen, and Hongling Gu, and Na Li, and Junru Wang
November 2022, Fitoterapia,
Hongtao Du, and Shan Tian, and Juncheng Chen, and Hongling Gu, and Na Li, and Junru Wang
January 2019, Frontiers in chemistry,
Hongtao Du, and Shan Tian, and Juncheng Chen, and Hongling Gu, and Na Li, and Junru Wang
October 2021, Molecules (Basel, Switzerland),
Hongtao Du, and Shan Tian, and Juncheng Chen, and Hongling Gu, and Na Li, and Junru Wang
August 2018, Molecules (Basel, Switzerland),
Hongtao Du, and Shan Tian, and Juncheng Chen, and Hongling Gu, and Na Li, and Junru Wang
December 2020, Archiv der Pharmazie,
Hongtao Du, and Shan Tian, and Juncheng Chen, and Hongling Gu, and Na Li, and Junru Wang
October 2014, European journal of medicinal chemistry,
Hongtao Du, and Shan Tian, and Juncheng Chen, and Hongling Gu, and Na Li, and Junru Wang
January 2022, Bioorganic & medicinal chemistry letters,
Hongtao Du, and Shan Tian, and Juncheng Chen, and Hongling Gu, and Na Li, and Junru Wang
February 2018, Bioorganic & medicinal chemistry letters,
Hongtao Du, and Shan Tian, and Juncheng Chen, and Hongling Gu, and Na Li, and Junru Wang
June 2023, Fitoterapia,
Hongtao Du, and Shan Tian, and Juncheng Chen, and Hongling Gu, and Na Li, and Junru Wang
March 2024, Anticancer research,
Copied contents to your clipboard!