Synthesis and in vitro evaluation of 3h-pyrrolo[3,2-f]-quinolin-9-one derivatives that show potent and selective anti-leukemic activity.

ChemMedChem
Maria Grazia FerlinGiampietro Viola

Abstract

A series of new substituted 7-phenyl-3H-pyrrolo[3,2-f]quinolin-9-ones were synthesized and evaluated for their antiproliferative activity. The most active derivatives showed high selectivity against human leukemia cell lines and potently inhibited their growth, with GI(50) values in the nanomolar range. The active compounds strongly blocked tubulin assembly and colchicine binding to tubulin. Their activities were equal to or greater than that of the reference compound combretastatin A-4. Flow cytometry studies showed that the two most active compounds arrested Jurkat cells in the G(2)/M cell-cycle phase in a concentration-dependent manner. This effect was associated with apoptosis, mitochondrial depolarization, generation of reactive oxygen species, activation of caspase-3, and cleavage of the enzyme poly(ADP-ribose) polymerase.

References

Aug 1, 1997·Nature Genetics·C M Knudson, S J Korsmeyer
Dec 5, 1998·Bioorganic & Medicinal Chemistry·L J HuangS C Kuo
Oct 3, 1999·Journal of Medicinal Chemistry·T OwaK Kitoh
Jun 29, 2000·Annual Review of Biochemistry·W C EarnshawS H Kaufmann
Jul 9, 2002·Apoptosis : an International Journal on Programmed Cell Death·C Soldani, A Ivana Scovassi
Dec 12, 2002·Chemical Reviews·Jean-Bernard Denault, Guy S Salvesen
May 27, 2003·Apoptosis : an International Journal on Programmed Cell Death·J D LyA Lawen
Sep 17, 2003·Apoptosis : an International Journal on Programmed Cell Death·F Mollinedo, C Gajate
Aug 3, 2004·Science·Douglas R Green, Guido Kroemer
Feb 16, 2005·Biochemical Pharmacology·Hans NohlKatrin Staniek
Apr 29, 2005·Journal of Medicinal Chemistry·Maria Grazia FerlinIgnazio Castagliuolo
Oct 6, 2007·Journal of Medicinal Chemistry·Venusia GasparottoMaria Grazia Ferlin
Mar 3, 2009·Bioorganic & Medicinal Chemistry Letters·Romeo RomagnoliGiampietro Viola

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