title: p,p-Dihydroxydihydrostilbenophanes related to antimitotic combretastatins. Conformational analysis and its relationship to tubulin inhibition.
abstract: The structures of a new family of macrocyclic analogues of combretastatins B combining oxygenated substituents on the phenyl rings and indole rings are described. The effects of the stereochemistry, of the length of the spacer linking both aryl groups, and of the decoration of the macrocycles on the kinematics of the system have been studied by means of NMR studies at several temperatures and in different solvents combined with theoretical studies including Monte Carlo conformational searches and molecular dynamics simulations at different temperatures. The new indole macrocycles provide a more rigid view of this kind of macrocycles than that previously held. The tubulin polymerization activity of this new class of macrocycles has been assayed and analyzed.
authors: Laboratorio de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad de Salamanca , Campus Miguel de Unamuno, E-37007 Salamanca, Spain.
authors: Raquel
authors: R
authors: Álvarez
authors: Vilmarí
authors: V
authors: López
authors: Carmen
authors: C
authors: Mateo
authors: Manuel
authors: M
authors: Medarde
authors: Rafael
authors: R
authors: Peláez
mesh_terms: D050256:Antimitotic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001632:Bibenzyls / Q000737:chemistry* / Q000494:pharmacology*; D003078:Colchicine / Q000737:chemistry*; D047028:Macrocyclic Compounds / Q000737:chemistry* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D058105:Polymerization; D013267:Stilbenes / Q000737:chemistry* / Q000494:pharmacology*; D050257:Tubulin Modulators / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D050256:Antimitotic Agents; D001632:Bibenzyls; D047028:Macrocyclic Compounds; D013267:Stilbenes; D050257:Tubulin Modulators; C504774:stilbenophane; C040105:combretastatin; D003078:Colchicine