Chemistry Reference
In-Depth Information
Scheme 6.1
Structure of abietic acid (
1
) and dehydroabietic acid (
2
)
Nowadays selectivity index (SI) values are used to evaluate many biological activities
because they can be therapeutically relevant for designing and synthesising new
drugs [13]. Carboxylic derivatives of rosin acids such as methyl ester, alcohol and
aldehyde derivatives of abietic acid exhibited cytotoxic activity to some tumour
cells. Abietic acid can be esterified by treatment with lithium hydroxide and methyl
sulfate. Reduction of the ester with lithium aluminium hydride in tetrahydrofuran
produced an alcohol and oxidation of the alcohol by treatment with pyridinium
chlorochromate on alumina afforded the corresponding aldehyde. The antitumour
activities of abietic acid derivatives were investigated using their SI values [14]. These
compounds produced a dose-dependent inhibition on the growth of the HeLa tumour
cell line and Vero cell line (
Table 6.1
). The ester of abietic acid (
3
) showed the highest
potential antitumour activity on the HeLa tumour line and the lowest cytotoxicity
on the Vero cell line, with 50% cytotoxicity concentration (CC
50
) values of 3.6 ± 1
μg/mL and 49.4 ± 3 μg/mL, respectively. The abietane with the highest SI was methyl
abietate, with an SI value of 13.7. An SI value of 14.3 on cell lines is indicative of
potential antitumour activity for biopharmaceutical use. According to SI values in
Figure 6.1
, the order of activity in the abietane series (
1
and
3
-
5
) was found to be
ester> aldehyde> acid> alcohol. On the other hand, the antitumour activity data in
the series of abietanes (
6
-
9
) indicated a significant reduction of activity, dependent
on the isomerisation of the two double bonds (
Scheme 6.2
).
Scheme 6.2
Structure of antitumour compounds (
3
-
9
)
