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New antitubulin derivatives in the combretastatin A4 series: synthesis and biological evaluation. 2005

Christine Borrel, and Sylviane Thoret, and Xavier Cachet, and Daniel Guénard, and François Tillequin, and Michel Koch, and Sylvie Michel
Laboratoire de Pharmacognosie, Université René Descartes (Paris 5), CNRS UMR 8638, Faculté des Sciences Pharmaceutiques et Biologiques, 4 avenue de l'Observatoire, 75270 Paris cedex 06, France.

Two series of combretastatin A4 derivatives (acrylamide=carboxamide and carbamate) were synthesized in order to improve the water solubility and stabilize the cis-configuration of the double bond. Their cytotoxic effects were evaluated against MCF-7, KB-3-1 and IGROV human cancer cell lines, as well as their inhibitory activity on tubulin polymerization. Results were compared to those of carboxamide 1, chosen as reference. Potent inhibitions were observed on both tests in the carboxamide series, particularly for compound 4d bearing a fluorine group in replacement of the 3-hydroxyl of CA4. In contrast, most of the carbamates were either inactive or displayed only moderate cytotoxicities. Interestingly, a submicromolar IC(50) was measured on MCF-7 cells for 6g, although this compound was totally devoid of antitubulin activity.

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
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001704 Biopolymers Polymers synthesized by living organisms. They play a role in the formation of macromolecular structures and are synthesized via the covalent linkage of biological molecules, especially AMINO ACIDS; NUCLEOTIDES; and CARBOHYDRATES. Bioplastics,Bioplastic,Biopolymer
D013057 Spectrum Analysis The measurement of the amplitude of the components of a complex waveform throughout the frequency range of the waveform. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed) Spectroscopy,Analysis, Spectrum,Spectrometry
D013267 Stilbenes Organic compounds that contain 1,2-diphenylethylene as a functional group. Stilbene,Stilbene Derivative,Stilbene Derivatives,Stilbenoid,Stilbenoids,Derivative, Stilbene,Derivatives, Stilbene
D014404 Tubulin A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from SPERM FLAGELLUM; CILIA; and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to COLCHICINE; VINCRISTINE; and VINBLASTINE. alpha-Tubulin,beta-Tubulin,delta-Tubulin,epsilon-Tubulin,gamma-Tubulin,alpha Tubulin,beta Tubulin,delta Tubulin,epsilon Tubulin,gamma Tubulin
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
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

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