Arylthioindole Inhibitors of Tubulin Polymerization. 3. Biological Evaluation, Structure-Activity Relationships and Molecular Modeling Studies. (Articolo in rivista)

Type
Label
  • Arylthioindole Inhibitors of Tubulin Polymerization. 3. Biological Evaluation, Structure-Activity Relationships and Molecular Modeling Studies. (Articolo in rivista) (literal)
Anno
  • 2007-01-01T00:00:00+01:00 (literal)
Alternative label
  • La Regina G, Edler MC, Brancale A, Kandil S, Piscitelli F, Hamel E, De Martino G, Matesanz R, Díaz JF, Scovassi AI, Prosperi E, Lavecchia A, Novellino E, Artico M, Silvestri R. (2007)
    Arylthioindole Inhibitors of Tubulin Polymerization. 3. Biological Evaluation, Structure-Activity Relationships and Molecular Modeling Studies.
    in Journal of medicinal chemistry
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • La Regina G, Edler MC, Brancale A, Kandil S, Piscitelli F, Hamel E, De Martino G, Matesanz R, Díaz JF, Scovassi AI, Prosperi E, Lavecchia A, Novellino E, Artico M, Silvestri R. (literal)
Pagina inizio
  • 2865 (literal)
Pagina fine
  • 2874 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 50 (literal)
Rivista
Note
  • Scopu (literal)
  • ISI Web of Science (WOS) (literal)
  • PubMe (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Istituto Pasteur – Fondazione Cenci Bolognetti, Dipartimento di Studi Farmaceutici, Sapienza Università di Roma, Piazzale Aldo Moro 5, I-00185 Roma, Italy, Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff, CF10 3XF, UK, Toxicology and Pharmacology Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute at Frederick, National Institutes of Health, Frederick, Maryland 21702, Dipartimento di Chimica Farmaceutica e Tossicologica, Università di Napoli “Federico II”, Via Domenico Montesano 49, I-80131, Napoli, Italy, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Cientificas, C/ Ramiro de Maeztu 9, E-28040 Madrid, Spain, Istituto di Genetica Molecolare – Consiglio Nazionale delle Ricerche, Via Abbiategrasso 207, I-27100 Pavia, Italy. (literal)
Titolo
  • Arylthioindole Inhibitors of Tubulin Polymerization. 3. Biological Evaluation, Structure-Activity Relationships and Molecular Modeling Studies. (literal)
Abstract
  • The new arylthioindole (ATI) derivatives 10, 14-18, and 21-24, which bear a halogen atom or a small size ether group at position 5 of the indole moiety, were compared with the reference compounds colchicine and combretastatin A-4 for biological activity. Derivatives 10, 11, 16, and 21-24 inhibited MCF-7 cell growth with IC50 values <50 nM. A halogen atom (14-17) at position 5 caused a significant reduction in the free energy of binding of compound to tubulin, with a concomitant reduction in cytotoxicity. In contrast, methyl (21) and methoxy (22) substituents at position 5 caused an increase in cytotoxicity. Compound 16, the most potent antitubulin agent, led to a large increase (56%) in HeLa cells in the G2/M phase at 24 h, and at 48 h, 26% of the cells were hyperploid. Molecular modeling studies showed that, despite the absence of the ester moiety present in the previously examined analogues, most of the compounds bind in the colchicine site in the same orientation as the previously studied ATIs. Binding to beta-tubulin involved formation of a hydrogen bond between the indole and Thr179 and positioning of the trimethoxy phenyl group in a hydrophobic pocket near Cys241. (literal)
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