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
Nov 1, 1995·The Journal of Experimental Medicine·S J MartinD R Green
Jul 17, 1995·Journal of Immunological Methods·I VermesC Reutelingsperger
Aug 1, 1995·The Journal of Experimental Medicine·N ZamzamiG Kroemer
Feb 21, 1997·Science·R M KluckD D Newmeyer
Aug 1, 1997·Nature Genetics·C M Knudson, S J Korsmeyer
Jul 7, 1997·FEBS Letters·S SalvioliA Cossarizza
Jan 28, 1998·Molecular Pharmacology·P Verdier-PinardE Hamel
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
Mar 29, 2003·Cell Biochemistry and Biophysics·Ernest Hamel
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
Mar 17, 2006·Journal of Medicinal Chemistry·Venusia GasparottoMaria Grazia Ferlin
Oct 6, 2007·Journal of Medicinal Chemistry·Venusia GasparottoMaria Grazia Ferlin
Mar 3, 2009·Bioorganic & Medicinal Chemistry Letters·Romeo RomagnoliGiampietro Viola
Apr 14, 2009·Cancer Chemotherapy and Pharmacology·Giampietro ViolaGirolamo Cirrincione
Citations
Sep 13, 2013·Journal of Medicinal Chemistry·Maria Grazia FerlinGiampietro Viola
Mar 11, 2015·European Journal of Medicinal Chemistry·Ramineni VenkateshManikapal Bhadra
Jan 13, 2012·European Journal of Medicinal Chemistry·Maria Grazia FerlinRenzo Deana
Oct 9, 2015·ChemMedChem·Davide CartaMaria Grazia Ferlin
Sep 30, 2015·Journal of Medicinal Chemistry·Davide CartaMaria Grazia Ferlin
May 23, 2016·Bioorganic & Medicinal Chemistry Letters·Jyothsna Devi PalemVijjulatha Manga