Synthesis and biological activity of 7-phenyl-6,9-dihydro-3H-pyrrolo[3,2-f]quinolin-9-ones: a new class of antimitotic agents devoid of aromatase activity.
The newly synthesized 7-phenyl-3H-pyrrolo[3,2-f]quinolinones 16-26 and previously 27 and 28 were assayed for their in vitro antiproliferative activity on tumor cell lines, and the lead compound 16 in vivo on a singenic hepatocellular carcinoma in Balb/c mice. Results from FACS, immunofluorescence microscopy analysis, tubulin polymerization assay, and tritiated water release assay for the CYP19 activity confirmed the new compounds as potential anticancer agents acting by tubulin depolymerization, but devoid of aromatase activity unlike their geometric [2,3-h] isomers.
Department of Pharmaceutical Sciences, University of Padova, 35131 Padova, Italy.
Venusia
V
Gasparotto
Ignazio
I
Castagliuolo
Gianfranco
G
Chiarelotto
Vincenzo
V
Pezzi
Daniela
D
Montanaro
Paola
P
Brun
Giorgio
G
Palù
Giampietro
G
Viola
Maria Grazia
MG
Ferlin
D000818:Animals; D050256:Antimitotic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001141:Aromatase / Q000378:metabolism*; D001704:Biopolymers; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D008856:Microscopy, Fluorescence; D009368:Neoplasm Transplantation; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014185:Transplantation, Isogeneic; D014316:Tritium; D014404:Tubulin / Q000737:chemistry; D014867:Water / Q000378:metabolism
C509858:7-phenyl-6,9-dihydro-3H-pyrrolo(3,2-f)quinolin-9-one; D050256:Antimitotic Agents; D001704:Biopolymers; D011758:Pyrroles; D015363:Quinolones; D014404:Tubulin; D014867:Water; D014316:Tritium; D001141:Aromatase