Biomaterial Database

Synthesis, biological evaluation of 1,1-diarylethylenes as a novel class of antimitotic agents. 2009

Abdallah Hamze, and Anne Giraud, and Samir Messaoudi, and Olivier Provot, and Jean-François Peyrat, and Jérôme Bignon, and Jian-Miao Liu, and Joanna Wdzieczak-Bakala, and Sylviane Thoret, and Joëlle Dubois, and Jean-Daniel Brion, and Mouad Alami

Université Paris-Sud, CNRS, BioCIS-UMR, Châtenay-Malabry, France.

The cytotoxic activities of 23 new isocombretastatin A derivatives with modifications on the B-ring were investigated. Several compounds exhibited excellent antiproliferative activity at nanomolar concentrations against a panel of human cancer cell lines. Compounds isoFCA-4 (2 e), isoCA-4 (2 k) and isoNH(2)CA-4 (2 s) were the most cytotoxic, and strongly inhibited tubulin polymerization with IC(50) values of 4, 2 and 1.5 microM, respectively. These derivatives were found to be 10-fold more active than phenstatin and colchicine with respect to growth inhibition but displayed similar activities as tubulin polymerization inhibitors. In addition, cell cycle arrest in the G(2)/M phase and subsequent apoptosis was observed in three cancer cell lines when treated with these compounds. The disruptive effect of 2 e, 2 k and 2 s on the vessel-like structures formed by human umbilical vein endothelial cells (HUVEC) suggest that these compounds may act as vascular disrupting agents. Both compounds 2 k and 2 s have the potential for further prodrug modification and development as vascular disrupting agents for treatment of solid tumors.

UI	MeSH Term	Description	Entries
D010755	Organophosphates	Carbon-containing phosphoric acid derivatives. Included under this heading are compounds that have CARBON atoms bound to one or more OXYGEN atoms of the P(	Organophosphate,Phosphates, Organic,Phosphoric Acid Esters,Organopyrophosphates,Acid Esters, Phosphoric,Esters, Phosphoric Acid,Organic Phosphates
D002455	Cell Division	The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.	M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D003078	Colchicine	A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (PERIODIC DISEASE).	Colchicine, (+-)-Isomer,Colchicine, (R)-Isomer
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001577	Benzophenones	Derivatives of benzophenone (with the structural formula phenyl-(C
D013267	Stilbenes	Organic compounds that contain 1,2-diphenylethylene as a functional group.	Stilbene,Stilbene Derivative,Stilbene Derivatives,Stilbenoid,Stilbenoids,Derivative, Stilbene,Derivatives, Stilbene
D016195	G2 Phase	The period of the CELL CYCLE following DNA synthesis (S PHASE) and preceding M PHASE (cell division phase). The CHROMOSOMES are tetraploid in this point.	Gap Phase 2,Second Gap Phase,G2 Phases,Gap Phase, Second,Gap Phases, Second,Phase 2, Gap,Phase, G2,Phase, Second Gap,Phases, G2,Phases, Second Gap,Second Gap Phases
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
D050256	Antimitotic Agents	Agents that arrest cells in MITOSIS, most notably TUBULIN MODULATORS.	Antimitotic,Antimitotic Agent,Antimitotic Drug,Antimitotic Drugs,Antimitotics,Agent, Antimitotic,Agents, Antimitotic,Drug, Antimitotic,Drugs, Antimitotic
D050257	Tubulin Modulators	Agents that interact with TUBULIN to inhibit or promote polymerization of MICROTUBULES.	Microtubule Modulator,Tubulin Inhibitor,Tubulin Modulator,Tubulin Polymerization Inhibitor,Tubulin Polymerization Promoter,Tubulin Promoter,Microtubule Modulators,Tubulin Inhibitors,Tubulin Polymerization Inhibitors,Tubulin Polymerization Promoters,Tubulin Promoters,Inhibitor, Tubulin,Inhibitor, Tubulin Polymerization,Inhibitors, Tubulin,Inhibitors, Tubulin Polymerization,Modulator, Microtubule,Modulator, Tubulin,Modulators, Microtubule,Modulators, Tubulin,Polymerization Inhibitor, Tubulin,Polymerization Inhibitors, Tubulin,Polymerization Promoter, Tubulin,Polymerization Promoters, Tubulin,Promoter, Tubulin,Promoter, Tubulin Polymerization,Promoters, Tubulin,Promoters, Tubulin Polymerization