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.

La Regina, G., Bai, R., Coluccia, A., Naccarato, V., Famiglini, V., Nalli, M., Masci, D., Verrico, A., Rovella, P., Mazzoccoli, C., Da Pozzo, E., Cavallini, C., Martini, M. C., Vultaggio, S., Dondio, G., Varasi, M., Mercurio, C., Hamel, E., Lavia, P., Silvestri, R., New 6- and 7-heterocyclyl-1H-indole derivatives as potent tubulin assembly and cancer cell growth inhibitors, <<EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY>>, 2018; 152 (May): 283-297. [doi:10.1016/j.ejmech.2018.04.042] [https://hdl.handle.net/10807/195403]

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

La Regina, Giuseppe
Primo
Writing – Original Draft Preparation
;
Masci, Domiziana
Writing – Review & Editing
;
Martini, Maria Cristina;
2018

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.
2018
Inglese
La Regina, G., Bai, R., Coluccia, A., Naccarato, V., Famiglini, V., Nalli, M., Masci, D., Verrico, A., Rovella, P., Mazzoccoli, C., Da Pozzo, E., Cavallini, C., Martini, M. C., Vultaggio, S., Dondio, G., Varasi, M., Mercurio, C., Hamel, E., Lavia, P., Silvestri, R., New 6- and 7-heterocyclyl-1H-indole derivatives as potent tubulin assembly and cancer cell growth inhibitors, <<EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY>>, 2018; 152 (May): 283-297. [doi:10.1016/j.ejmech.2018.04.042] [https://hdl.handle.net/10807/195403]
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/195403
Citazioni
  • ???jsp.display-item.citation.pmc??? 7
  • Scopus 31
  • ???jsp.display-item.citation.isi??? 29
social impact