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Abstract
The semisynthesis and biological activity of the naturally occurring abietane diterpenoids callitrisic acid (
4a
; 4-epidehydroabietic acid) and callitrisinol (
6
) are reported. These compounds and jiadifenoic acid C (
5
) were obtained from methyl callitrisate (
4b
) isolated from Sandarac resin for biological evaluation and comparison with the biological activities of C4 epimers such as dehydroabietic acid (
2a
). In particular, the antiproliferative activity against a panel of six representative human solid tumor cell lines (A549, HBL-100, HeLa, SW1573, T-47D, WiDr) and the effect on GABA
A
receptors (
α
1
β
2
γ
2s
) were evaluated. The GI
50
values were in the range of 3.4–61 µM and the potentiation of I
GABA
was 269–311% at 100 µM. Callitrisinol (
6
) was found to be 6.7-fold more potent than the reference etoposide in the WiDr (colon) cancer cell line. The role of the stereogenic center at C4 for antiproliferative and GABA
A
receptor modulating activities in the dehydroabietane scaffold has thus been revealed.