Structural and biological investigation of ferrocene-substituted 3-methylidene-1,3-dihydro-2H-indol-2-ones.
The Knoevenagel condensation of 1,3-dihydro-2H-indol-2-one with ferrocene carboxaldehyde afforded an approximate 2:1 mixture of the geometrical isomers (E)- and (Z)-3-ferrocenylmethylidene-1,3-dihydro-2H-indol-2-one respectively in an overall 67% yield; the air and solution-stable isomers were readily separated by preparative thin layer chromatography and their structures were unequivocally elucidated in solution, by (1)H NMR spectroscopy, and in the solid phase, by X-ray crystallography; both isomers of displayed in vitro toxicity against B16 melanoma and Vero cell lines in the micromolar range and inhibited the kinase VEGFR-2 with IC(50) values of ca. 200 nM.
Spencer
John
J
School of Science, University of Greenwich at Medway, Chatham Maritime, UKME4 4TB. j.spencer@gre.ac.uk
Mendham
Andrew P
AP
Kotha
Arun K
AK
Richardson
Simon C W
SC
Hillard
Elizabeth A
EA
Jaouen
Gérard
G
Male
Louise
L
Hursthouse
Michael B
MB
D000818:Animals; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D018360:Crystallography, X-Ray; D005296:Ferrous Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D051379:Mice; D013237:Stereoisomerism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors; D014709:Vero Cells
C539307:3-ferrocenylmethylidene-1,3-dihydro-2H-indol-2-one; D005296:Ferrous Compounds; D007211:Indoles; C422706:ferrocenecarboxaldehyde; D040301:Vascular Endothelial Growth Factor Receptor-2