Research on multitargeting drugs is emerging, focusing on the discovery of agents that simultaneously act on more than one biological target. Here, a novel synthetic route to access the fused-heterocycles 1,4-dihydropyrazolo[4,3-b]indoles (4) from pyrazolo[4,3-c][2,1]benzothiazine 4,4-dioxide (3) via [H2O–SO2] elimination and an intramolecular ring-closing reaction is reported. Two lead compounds 3b and 4b were found to show significant inhibition of cell growth by suppressing cell cycle progression at the G0/G1 phases and inducing apoptosis of the acute myeloid leukemia OCI-AML3 cell line. Both compounds also significantly decreased tumor necrosis factor-α and transforming growth factor-β (at all tested concentrations), whereas no effect was seen on other cytokines (interleukin-4, interferon-γ, interleukin-9, interleukin-12). Thus, these compounds are promising leads in the discovery of novel anticancer agents.

New 1,4-Dihydropyrazolo[4,3-b]indoles Induce Antiproliferation of Acute Myeloid Leukemia Cells and Inhibition of Selective Inflammatory Cytokines

Adorisio S.;Delfino D. V.;
2022

Abstract

Research on multitargeting drugs is emerging, focusing on the discovery of agents that simultaneously act on more than one biological target. Here, a novel synthetic route to access the fused-heterocycles 1,4-dihydropyrazolo[4,3-b]indoles (4) from pyrazolo[4,3-c][2,1]benzothiazine 4,4-dioxide (3) via [H2O–SO2] elimination and an intramolecular ring-closing reaction is reported. Two lead compounds 3b and 4b were found to show significant inhibition of cell growth by suppressing cell cycle progression at the G0/G1 phases and inducing apoptosis of the acute myeloid leukemia OCI-AML3 cell line. Both compounds also significantly decreased tumor necrosis factor-α and transforming growth factor-β (at all tested concentrations), whereas no effect was seen on other cytokines (interleukin-4, interferon-γ, interleukin-9, interleukin-12). Thus, these compounds are promising leads in the discovery of novel anticancer agents.
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: http://hdl.handle.net/11391/1529993
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 0
  • ???jsp.display-item.citation.isi??? 0
social impact