Chemistry Reference
In-Depth Information
Cancer cells depend on glucolysis rather than oxidative phosphorylation for
generating adenosine triphosphate (ATP) whereas normal cells depend on oxidative
phosphorylation, especially in anaerobic condition [65]. Urea derivative of
dehydroabietic acid (
89
) (
Scheme 6.24
), a novel derivative of dehydroabietic acid,
showed a significant dose- and time-dependent inhibition of growth in both hypoxic
and normoxic cells. Their IC
50
values to both hypoxic and normoxic cells are below
10μM. The effects of (
89
) on cell viability and glucose metabolism in hypoxic and
normoxic human hepatoma HepG2 cells were investigated [66]. It was shown that
(
89
) markedly inhibited cell viability, cellular ATP level, lactate dehydrogenase and
glucose-6-phosphate dehydrogenase activity in either aerobic or anaerobic conditions
in a dose- and time-dependent manner. This suggested that (
89
) possibly inhibited
HepG2 cell growth via the inhibition of glucolysis and glucolysis-dependent ATP
depletion. (
89
) could be a promising candidate in the development of a novel class
of agents used for human hepatocellular carcinoma.
Scheme 6.24
Structure of urea derivative of dehydroabietic acid (
89
)
6.4.2 Anti-inflammatory Mechanism
Abietic acid (
1
) was reported to have an anti-inflammatory effect [45]. However,
the mechanism underlying this effect has not been clarified. Takahashi and co-
workers [67] investigated the mechanism of the anti-inflammatory effect of abietic
acid. It was reported that abietic acid suppressed the protein expression of tumour
necrosis factor-α and cyclooxygenase 2, which are involved in inflammation, in
lipopolysaccharide stimulated macrophages. Moreover, this effect resembles that of
thiazolidinedione, a synthetic peroxisome proliferator-activated receptor-Q (PPARQ)
ligand. Indeed, abietic acid activates PPARQ in luciferase reporter assays. The activity
