title: B-ring-modified isocombretastatin A-4 analogues endowed with interesting anticancer activities.
abstract: A novel class of isocombretastatin A-4 (isoCA-4) analogues with modifications at the 3'-position of the B-ring by replacement with C-linked substituents was studied. Exploration of the structure-activity relationships of theses analogues led to the identification of several compounds that exhibit excellent antiproliferative activities in the nanomolar concentration range against H1299, MDA-MB231, HCT116, and K562 cancer cell lines; they also inhibit tubulin polymerization with potency similar to that of isoCA-4. 1,1-Diarylethylenes 8 and 17, respectively with (E)-propen-3-ol and propyn-3-ol substituents at the 3'-position of the B-ring, proved to be the most active in this series. Both compounds led to the arrest of various cancer cell lines at the G(2) /M phase of the cell cycle and strongly induced apoptosis. Docking of compounds 8 and 17 in the colchicine binding site indicated that their C3' substituents guide the positioning of the B-ring in a manner different from that observed for isoCA-4.
authors: Université Paris-Sud, CNRS, BioCIS-UMR 8076, Laboratoire de Chimie Thérapeutique, Faculté de Pharmacie, 5 rue J.-B. Clément, Châtenay-Malabry, 92296, France.
authors: Abdallah
authors: A
authors: Hamze
authors: Evelia
authors: E
authors: Rasolofonjatovo
authors: Olivier
authors: O
authors: Provot
authors: Céline
authors: C
authors: Mousset
authors: Damien
authors: D
authors: Veau
authors: Jordi
authors: J
authors: Rodrigo
authors: Jérôme
authors: J
authors: Bignon
authors: Jian-Miao
authors: JM
authors: Liu
authors: Joanna
authors: J
authors: Wdzieczak-Bakala
authors: Sylviane
authors: S
authors: Thoret
authors: Joëlle
authors: J
authors: Dubois
authors: Jean-Daniel
authors: JD
authors: Brion
authors: Mouad
authors: M
authors: Alami
mesh_terms: D000840:Anisoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003198:Computer Simulation; D006801:Humans; D009369:Neoplasms; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D013343:Styrenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: C571074:3-(2-methoxy-5-(1-(3,4,5-trimethoxyphenyl)vinyl)phenyl)prop-2-en-1-ol; C571075:3-(2-methoxy-5-(1-(3,4,5-trimethoxyphenyl)vinyl)phenyl)prop-2-yn-1-ol; D000840:Anisoles; D000970:Antineoplastic Agents; D013343:Styrenes; D014404:Tubulin; D050257:Tubulin Modulators