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New 6- and 7-heterocyclyl-1H-indole derivatives as potent tubulin assembly and cancer cell growth inhibitors

  1. Author:
    La Regina, Giuseppe
    Bai, Ruoli
    Coluccia, Antonio
    Naccarato, Valentina
    Famiglini, Valeria
    Nalli, Marianna
    Masci, Domiziana
    Verrico, Annalisa
    Rovella, Paola
    Mazzoccoli, Carmela
    Da Pozzo, Eleonora
    Cavallini, Chiara
    Martini, Claudia
    Vultaggio, Stefania
    Dondio, Giulio
    Varasi, Mario
    Mercurio, Ciro
    Hamel, Ernest
    Lavia, Patrizia
    Silvestri, Romano

  2. Author Address

    Department of Drug Chemistry and Technologies, Sapienza University of Rome, Laboratory Affiliated to Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Piazzale Aldo Moro 5, I-00185 Roma, Italy., Screening Technologies Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, United States., Institute of Molecular Biology and Pathology (IBPM), CNR Consiglio Nazionale Delle Ricerche, C/o Sapienza University of Rome, Via Degli Apuli 4, I-00185 Roma, Italy., Laboratorio di Ricerca Pre-Clinica e Traslazionale, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Centro di Riferimento Oncologico Della Basilicata, Via Padre Pio 1, I-85028, Rionero in Vulture, Italy., Department of Pharmacy, University of Pisa, Via Bonanno Pisano 6, I-56126 Pisa, Italy., Experimental Therapeutics IFOM-the FIRC Institute of Molecular Oncology Foundation, Via Adamello 16, 20139 Milan, Italy., APHAD, Via Della Resistenza 65, 20090 Buccinasco MI, Italy., Department of Drug Chemistry and Technologies, Sapienza University of Rome, Laboratory Affiliated to Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Piazzale Aldo Moro 5, I-00185 Roma, Italy. Electronic address: romano.silvestri@uniroma1.it.,
    1. Year: 2018
    2. Date: May 25
    3. Epub Date: 2018 04 25
  2. Journal: European Journal of Medicinal Chemistry
    1. 152
    2. Pages: 283-297
  4. Type of Article: Article
  1. Abstract:

    We designed new 3-arylthio- and 3-aroyl-1H-indole derivatives 3-22 bearing a heterocyclic ring at position 5, 6 or 7 of the indole nucleus. The 6- and 7-heterocyclyl-1H-indoles showed potent inhibition of tubulin polymerization, binding of colchicine to tubulin and growth of MCF-7 cancer cells. Compounds 13 and 19 inhibited a panel of cancer cells and the NCI/ADR-RES multidrug resistant cell line at low nanomolar concentrations. Compound 13?at 50?nM induced 77% G2/M in HeLa cells, and at 20?nM caused 50% stable arrest of mitosis. As an inhibitor of HepG2 cells (IC50?=?20?nM), 13 was 4-fold superior to 19. Compound 13 was a potent inhibitor of the human U87MG glioblastoma cells at nanomolar concentrations, being nearly one order of magnitude superior to previously reported arylthioindoles. The present results highlight 13 as a robust scaffold for the design of new anticancer agents. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.ejmech.2018.04.042
  3. PMID: 29730191
  4. View record in Web of Science®
  5. WOS: 000435048900023
  6. PII : S0223-5234(18)30376-3

Library Notes

  1. Fiscal Year: FY2017-2018
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