Synthesis and antiproliferative activity of substituted 3[2-(1h-indol-3-yl)- 1,3-thiazol-4-yl]-1h-pyrrolo[3,2-b]pyridines, marine alkaloid nortopsentin analogues

A. Carbone, M. Pennati, P. Barraja, A. Montalbano, B. Parrino, V. Spanò, A. Lopergolo, S. Sbarra, V. Doldi, N. Zaffaroni, G. Cirrincione, P. Diana

Research output: Contribution to journalArticle

Abstract

A large number of indolyl-4-azaindolyl thiazoles, nortopsentin analogues, were conveniently synthesized. The antiproliferative activity of the new derivatives was examined against four human tumor cell lines with different histologic origin. Seven derivatives consistently reduced the growth of the experimental models independently of TP53 gene status and exhibited the highest activity against the malignant peritoneal mesothelioma (STO) cell line. The most active compound of this series acts as a CDK1 inhibitor, and was found to cause cell cycle arrest at G2/M phase, to induce apoptosis by preventing the phosphorylation of survivin in Thr34 and to increase the cytotoxic activity of paclitaxel in STO cells.

Original languageEnglish
Pages (from-to)1654-1666
Number of pages13
JournalCurrent Medicinal Chemistry
Volume21
Issue number14
DOIs
Publication statusPublished - 2014

Fingerprint

Pyridines
Thiazoles
G2 Phase
p53 Genes
Paclitaxel
Cell Cycle Checkpoints
Tumor Cell Line
Alkaloids
Cell Division
Theoretical Models
Cells
Phosphorylation
Apoptosis
Cell Line
Growth
Derivatives
Tumors
Genes
Malignant Mesothelioma

Keywords

  • Antiproliferative activity
  • CDK1 inhibitors
  • Diffuse malignant peritoneal mesothelioma
  • Indolyl-4-azaindolyl thiazoles
  • Nortopsentin analogues
  • Survivin

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Medicine(all)

Cite this

Synthesis and antiproliferative activity of substituted 3[2-(1h-indol-3-yl)- 1,3-thiazol-4-yl]-1h-pyrrolo[3,2-b]pyridines, marine alkaloid nortopsentin analogues. / Carbone, A.; Pennati, M.; Barraja, P.; Montalbano, A.; Parrino, B.; Spanò, V.; Lopergolo, A.; Sbarra, S.; Doldi, V.; Zaffaroni, N.; Cirrincione, G.; Diana, P.

In: Current Medicinal Chemistry, Vol. 21, No. 14, 2014, p. 1654-1666.

Research output: Contribution to journalArticle

Carbone, A. ; Pennati, M. ; Barraja, P. ; Montalbano, A. ; Parrino, B. ; Spanò, V. ; Lopergolo, A. ; Sbarra, S. ; Doldi, V. ; Zaffaroni, N. ; Cirrincione, G. ; Diana, P. / Synthesis and antiproliferative activity of substituted 3[2-(1h-indol-3-yl)- 1,3-thiazol-4-yl]-1h-pyrrolo[3,2-b]pyridines, marine alkaloid nortopsentin analogues. In: Current Medicinal Chemistry. 2014 ; Vol. 21, No. 14. pp. 1654-1666.
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abstract = "A large number of indolyl-4-azaindolyl thiazoles, nortopsentin analogues, were conveniently synthesized. The antiproliferative activity of the new derivatives was examined against four human tumor cell lines with different histologic origin. Seven derivatives consistently reduced the growth of the experimental models independently of TP53 gene status and exhibited the highest activity against the malignant peritoneal mesothelioma (STO) cell line. The most active compound of this series acts as a CDK1 inhibitor, and was found to cause cell cycle arrest at G2/M phase, to induce apoptosis by preventing the phosphorylation of survivin in Thr34 and to increase the cytotoxic activity of paclitaxel in STO cells.",
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AU - Pennati, M.

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