title: New arylthioindoles and related bioisosteres at the sulfur bridging group. 4. Synthesis, tubulin polymerization, cell growth inhibition, and molecular modeling studies.
abstract: New arylthioindoles along with the corresponding ketone and methylene compounds were potent tubulin assembly inhibitors. As growth inhibitors of MCF-7 cells, sulfur derivatives were superior or sometimes equivalent to the ketones, while methylene derivatives were substantially less effective. Esters 24, 27-29, 36, 39, and 41 showed approximately 50% of inhibition on human HeLa and HCT116/chr3 cells at 0.5 microM, and these compounds inhibited the growth of HEK, M14, and U937 cells with IC(50)'s in the 78-220 nM range. While murine macrophage J744.1 cell growth was significantly less affected (20% at higher concentrations), four other nontransformed cell lines remained sensitive to these esters. The effect of drug treatment on cell morphology was examined by time-lapse microscopy. In a protocol set up to evaluate toxicity on the Saccharomyces cerevisiae BY4741 wild type strain, compounds 24 and 54 strongly reduced cell growth, and 29, 36, and 39 also showed significant inhibition.
authors: Dipartimento di Chimica e Tecnologie del Farmaco, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza Università di Roma, Piazzale Aldo Moro 5, I-00185 Roma, Italy.
authors: Giuseppe
authors: G
authors: La Regina
authors: Taradas
authors: T
authors: Sarkar
authors: Ruoli
authors: R
authors: Bai
authors: Michael C
authors: MC
authors: Edler
authors: Roberto
authors: R
authors: Saletti
authors: Antonio
authors: A
authors: Coluccia
authors: Francesco
authors: F
authors: Piscitelli
authors: Lara
authors: L
authors: Minelli
authors: Valerio
authors: V
authors: Gatti
authors: Carmela
authors: C
authors: Mazzoccoli
authors: Vanessa
authors: V
authors: Palermo
authors: Cristina
authors: C
authors: Mazzoni
authors: Claudio
authors: C
authors: Falcone
authors: Anna Ivana
authors: AI
authors: Scovassi
authors: Vincenzo
authors: V
authors: Giansanti
authors: Pietro
authors: P
authors: Campiglia
authors: Amalia
authors: A
authors: Porta
authors: Bruno
authors: B
authors: Maresca
authors: Ernest
authors: E
authors: Hamel
authors: Andrea
authors: A
authors: Brancale
authors: Ettore
authors: E
authors: Novellino
authors: Romano
authors: R
authors: Silvestri
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003078:Colchicine / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D055503:Protein Multimerization / Q000187:drug effects*; D020836:Protein Structure, Quaternary; D013329:Structure-Activity Relationship; D013455:Sulfur / Q000737:chemistry*; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism*
chemical_list: D007211:Indoles; D014404:Tubulin; D013455:Sulfur; D003078:Colchicine