Biomaterial Database

Synthesis, biological activity and mechanism of action of novel allosecurinine derivatives as potential antitumor agents. 2023

Xin-Liang Xu, and Jin-Xia Lan, and Hao Huang, and Wei Dai, and Xiao-Peng Peng, and Sheng-Lan Liu, and Wei-Ming Chen, and Le-Jun Huang, and Jun Liu, and Xiao-Jun Li, and Jun-Lin Zeng, and Xian-Hua Huang, and Guan-Nan Zhao, and Wen Hou

College of Pharmacy, Gannan Medical University, Ganzhou 341000, PR China.

Cancer with low survival rates is the second main cause of death among all diseases in the world and consequently, effective antineoplastic agents are urgently needed. Allosecurinine is a plant-derived indolicidine securinega alkaloid shown bioactivity. The object of this study is to investigate synthetic allosecurinine derivatives with considerable anticancer capacity against nine human cancer cell lines as well as mechanism of action. We synthesized twenty-three novel allosecurinine derivatives and evaluated their antitumor activity against nine cancer cell lines for 72 h by MTT and CCK8 assays. FCM was applied to analyze the apoptosis, mitochondrial membrane potential, DNA content, ROS production, CD11b expression. Western blot was selected to analyze the protein expression. Structure-activity relationships were established and potential anticancer lead BA-3 which induced differentiation of leukemia cells towards granulocytosis at low concentration and apoptosis at high concentration was identified. Mechanism studies showed that mitochondrial pathway mediated apoptosis within cancer cells with cell cycle blocking was induced by BA-3. In addition, western blot assays revealed that BA-3 induced expression of the proapoptotic factor Bax, p21 and reduced the levels of antiapoptotic protein such as Bcl-2, XIAP, YAP1, PARP, STAT3, p-STAT3, and c-Myc. Collectively, BA-3 was a lead compound for oncotherapy at least in part, through the STAT3 pathway. These results were an important step in further studies on allosecurinine-based antitumor agent development.

UI	MeSH Term	Description	Entries
D007783	Lactones	Cyclic esters of hydroxy carboxylic acids, containing a 1-oxacycloalkan-2-one structure. Large cyclic lactones of over a dozen atoms are MACROLIDES.	Lactone
D009369	Neoplasms	New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.	Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
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
D006572	Heterocyclic Compounds, Bridged-Ring	A class of organic compounds which contain two rings that share a pair of bridgehead carbon atoms.	Bridged-Ring Heterocyclic Compounds,Bridged Ring Heterocyclic Compounds,Compounds, Bridged-Ring Heterocyclic,Heterocyclic Compounds, Bridged Ring
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000470	Alkaloids	Organic nitrogenous bases. Many alkaloids of medical importance occur in the animal and vegetable kingdoms, and some have been synthesized. (Grant & Hackh's Chemical Dictionary, 5th ed)	Alkaloid,Plant Alkaloid,Plant Alkaloids,Alkaloid, Plant,Alkaloids, Plant
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
D001381	Azepines	Seven membered heterocyclic rings containing a NITROGEN atom.	Hexamethyleneimines
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