stilbenes and imidazole

Combretastatin A-4 (CA-4) is a natural cis-stilbene which interferes with the cellular tubulin dynamics and which selectively destroys tumour blood vessels. Its pharmacological shortcomings such as insufficient chemical stability, water solubility, and cytotoxicity can be remedied by employing its imidazole derivatives.. We studied 11 halogenated imidazole derivatives of CA-4 for their effects on the microtubule and actin cytoskeletons of cancer and endothelial cells and on the propensity of these cells to migrate across tissue barriers or to form blood vessel-like tubular structures.. A series of N-methyl-4-aryl-5-(4-ethoxyphenyl)-imidazoles proved far more efficacious than the lead CA-4 in growth inhibition assays against CA-4-resistant HT-29 colon carcinoma cells and generally more selective for cancer over nonmalignant cells. Et-brimamin (6), the most active compound, inhibited the growth of various cancer cell lines with IC50 (72 h) values in the low nanomolar range. Active imidazoles such as 6 reduced the motility and invasiveness of cancer cells by initiating the formation of actin stress fibres and focal adhesions as a response to the extensive microtubule disruption. The antimetastatic properties were ascertained in 3D-transwell migration assays which simulated the transgression of highly invasive melanoma cells through the extracellular matrix of solid tumours and through the endothelium of blood vessels. The studied imidazoles exhibited vascular-disrupting effects also against tumour xenografts that are refractory to CA-4. They were also less toxic and better tolerated by mice.. We deem the new imidazoles promising drug candidates for combination regimens with antiangiogenic VEGFR inhibitors.

Topics: Angiogenesis Inhibitors; Aniline Compounds; Animals; Antineoplastic Agents; Cell Cycle Checkpoints; Cell Death; Cell Line, Tumor; Cell Movement; Chickens; Collagen; Cytoskeleton; Drug Combinations; Human Umbilical Vein Endothelial Cells; Humans; Imidazoles; Laminin; Mice, Nude; Microtubules; Mitosis; Neoplasm Metastasis; Neovascularization, Physiologic; Proteoglycans; Stilbenes

A tetra-imidazole-appended tetrakis(p-phenylene)ethylene 1-Cu(2+) ensemble was found to enhance fluorescence upon addition of histidine, but not with any other amino acids. The 1-Cu(2+) ensemble also selectively detected proteins containing histidine residues in a mixture of water and methanol (90 : 10, v/v%). The 1-Cu(2+) ensemble-coated thin-layered chromatography (TLC) plate could also detect histidine quantitatively. Furthermore, the fluorescence emission recovery upon addition of five concentrations of His was ~80% with good linearity.

Topics: Chromatography, Thin Layer; Coordination Complexes; Copper; Histidine; Imidazoles; Spectrometry, Fluorescence; Stilbenes

Two new n-type diimidazolylstilbenes as blue-fluorescent dopant materials are synthesized and characterized. Blue-fluorescent devices based on these two compounds as the dopants reveal outstanding external quantum efficiencies (EQEs) (current efficiencies) of 7.8% (10.4 cd A(-1) ) and 7.7% (7.9 cd A(-1) ) with Commission internationale de l'Eclairage (CIE) co-ordinates of (0.14, 0.15) and (0.15, 0.11).

Topics: Fluorescent Dyes; Imidazoles; Luminescent Measurements; Quantum Theory; Stilbenes

Topics: Alkenes; Biomimetic Materials; Catalysis; Imidazoles; Iron; Oxidation-Reduction; Oxygen; Stilbenes; Temperature

The in vitro antitumor activity of novel combretastatin-like 1,5- and 1,2-diaryl-1H-imidazoles was evaluated against the NCI 60 human tumor cell lines panel. Compounds 2d and 2g proved to be more cytotoxic than CA-4 in tests involving their evaluation over a 10(-4)-10(-8) range. Docking experiments showed a good correlation between the MG_MID Log GI(50) values of all these compounds and their calculated interaction energies with the colchicine binding site of alphabeta-tubulin.

Topics: Antineoplastic Agents; Binding Sites; Cell Line, Tumor; Colchicine; Humans; Imidazoles; Stilbenes; Tubulin