New pyrrole derivatives with potent tubulin polymerization inhibiting activity as anticancer agents including hedgehog-dependent cancer

Giuseppe La Regina, Ruoli Bai, Antonio Coluccia, Valeria Famiglini, Sveva Pelliccia, Sara Passacantilli, Carmela Mazzoccoli, Vitalba Ruggieri, Lorenza Sisinni, Alessio Bolognesi, Whilelmina Maria Rensen, Andrea Miele, Marianna Nalli, Romina Alfonsi, Lucia Di Marcotullio, Alberto Gulino, Andrea Brancale, Ettore Novellino, Giulio Dondio, Stefania VultaggioMario Varasi, Ciro Mercurio, Ernest Hamel, Patrizia Lavia, Romano Silvestri

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

We synthesized 3-aroyl-1-arylpyrrole (ARAP) derivatives as potential anticancer agents having different substituents at the pendant 1-phenyl ring. Both the 1-phenyl ring and 3-(3,4,5-trimethoxyphenyl)carbonyl moieties were mandatory to achieve potent inhibition of tubulin polymerization, binding of colchicine to tubulin, and cancer cell growth. ARAP 22 showed strong inhibition of the P-glycoprotein-overexpressing NCI-ADR-RES and Messa/Dx5MDR cell lines. Compounds 22 and 27 suppressed in vitro the Hedgehog signaling pathway, strongly reducing luciferase activity in SAG treated NIH3T3 Shh-Light II cells, and inhibited the growth of medulloblastoma D283 cells at nanomolar concentrations. ARAPs 22 and 27 represent a new potent class of tubulin polymerization and cancer cell growth inhibitors with the potential to inhibit the Hedgehog signaling pathway.

Original languageEnglish
Pages (from-to)6531-6552
Number of pages22
JournalJournal of Medicinal Chemistry
Volume57
Issue number15
DOIs
Publication statusPublished - Aug 14 2014

Fingerprint

Pyrroles
Tubulin
Polymerization
Antineoplastic Agents
Neoplasms
Growth Inhibitors
Medulloblastoma
Colchicine
P-Glycoprotein
Growth
Luciferases
Light
Cell Line

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Medicine(all)

Cite this

La Regina, G., Bai, R., Coluccia, A., Famiglini, V., Pelliccia, S., Passacantilli, S., ... Silvestri, R. (2014). New pyrrole derivatives with potent tubulin polymerization inhibiting activity as anticancer agents including hedgehog-dependent cancer. Journal of Medicinal Chemistry, 57(15), 6531-6552. https://doi.org/10.1021/jm500561a

New pyrrole derivatives with potent tubulin polymerization inhibiting activity as anticancer agents including hedgehog-dependent cancer. / La Regina, Giuseppe; Bai, Ruoli; Coluccia, Antonio; Famiglini, Valeria; Pelliccia, Sveva; Passacantilli, Sara; Mazzoccoli, Carmela; Ruggieri, Vitalba; Sisinni, Lorenza; Bolognesi, Alessio; Rensen, Whilelmina Maria; Miele, Andrea; Nalli, Marianna; Alfonsi, Romina; Di Marcotullio, Lucia; Gulino, Alberto; Brancale, Andrea; Novellino, Ettore; Dondio, Giulio; Vultaggio, Stefania; Varasi, Mario; Mercurio, Ciro; Hamel, Ernest; Lavia, Patrizia; Silvestri, Romano.

In: Journal of Medicinal Chemistry, Vol. 57, No. 15, 14.08.2014, p. 6531-6552.

Research output: Contribution to journalArticle

La Regina, G, Bai, R, Coluccia, A, Famiglini, V, Pelliccia, S, Passacantilli, S, Mazzoccoli, C, Ruggieri, V, Sisinni, L, Bolognesi, A, Rensen, WM, Miele, A, Nalli, M, Alfonsi, R, Di Marcotullio, L, Gulino, A, Brancale, A, Novellino, E, Dondio, G, Vultaggio, S, Varasi, M, Mercurio, C, Hamel, E, Lavia, P & Silvestri, R 2014, 'New pyrrole derivatives with potent tubulin polymerization inhibiting activity as anticancer agents including hedgehog-dependent cancer', Journal of Medicinal Chemistry, vol. 57, no. 15, pp. 6531-6552. https://doi.org/10.1021/jm500561a
La Regina, Giuseppe ; Bai, Ruoli ; Coluccia, Antonio ; Famiglini, Valeria ; Pelliccia, Sveva ; Passacantilli, Sara ; Mazzoccoli, Carmela ; Ruggieri, Vitalba ; Sisinni, Lorenza ; Bolognesi, Alessio ; Rensen, Whilelmina Maria ; Miele, Andrea ; Nalli, Marianna ; Alfonsi, Romina ; Di Marcotullio, Lucia ; Gulino, Alberto ; Brancale, Andrea ; Novellino, Ettore ; Dondio, Giulio ; Vultaggio, Stefania ; Varasi, Mario ; Mercurio, Ciro ; Hamel, Ernest ; Lavia, Patrizia ; Silvestri, Romano. / New pyrrole derivatives with potent tubulin polymerization inhibiting activity as anticancer agents including hedgehog-dependent cancer. In: Journal of Medicinal Chemistry. 2014 ; Vol. 57, No. 15. pp. 6531-6552.
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AU - Novellino, Ettore

AU - Dondio, Giulio

AU - Vultaggio, Stefania

AU - Varasi, Mario

AU - Mercurio, Ciro

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AU - Lavia, Patrizia

AU - Silvestri, Romano

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