A selected set of substituted pyridone-annelated isoindigos
3a
–
f
has been synthesized via interaction of 5- and 6-substituted oxindoles
2a
–
f
with 6-ethyl-1,2,9-trioxopyrrolo[3,2-
f
]quinoline-8-carboxylic acid (
1
) in acetic acid at reflux. Among these isoindigos, the 5'-chloro and 5'-bromo derivatives
3b
and
3d
show strong and selective antiproliferative activities against a panel of human hematological and solid tumor cell-lines, but not against noncancerous cells, suggesting their potential use as anticancer agents. In all the tested cell lines, compound
3b
was a 25%–50% more potent inhibitor of cell growth than
3d
, suggesting the critical role of the substitution at 5'
-
position of the benzo-ring E. The IC
50
values after 48 hours incubation with the 5'-chloro compound
3b
were 6.60 µM in K562, 8.21 µM in THP-1, 8.97 µM in HepG2, 11.94 µM in MCF-7 and 14.59 µM in Caco-2 cancer cells, while the IC
50
values in noncancerous HEK-293 and L-929 were 30.65 µM and 40.40 µM, respectively. In addition, compound
3b
induced higher levels apoptosis in K562 cells than
3d
, as determined by annexin V/7-AAD flowcytometry analysis. Therefore, further characterization of the antitproliferative mechanisms of compounds
3b
and
3d
may provide a novel chemotherapeutic agents.
Schiff base diethyl 4,4-(pentane-2,4-diylidenebis(azanylylidene))benzoate (1) as a new ligand (L) was prepared by the reaction of acetylacetone with benzocaine in the ratio of 1 : 1. Two transition-metal complexes, [Ni(II)(LCl(HOEt))] (2) and [Zn(II)(LCl(HOEt))] (3), have been synthesized from metal salts with didentate Schiff base ligand (L) and characterized by elemental analyses, FT-IR, 1 H NMR, 13 C NMR UV-Vis spectroscopy, and magnetic susceptibility. e biological activity of the complexes was studied. In addition, the M06-2x density function theory method and the 6-31G(d) basic set were applied to determine the optimized structures of 1-3 and to determine their IR and 1 H NMR, 13 C NMR spectra theoretically. e data are in good agreement with the experimental results. e geometries of complexes 2 and 3 were determined to be square-planar for 2 and tetrahedral for 3.
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