Antiproliferative Activity and Effect on GABAA Receptors of Callitrisic Acid Derivatives

• Published in: Planta Medica International Open (Online) 2017-06, Vol.4 (3), p.e89-e92
• Main Authors: Stadler, Marco, Padrón, José M., González-Cardenete, Miguel A.
• Format: Article
• Language: English
• Subjects: Original Papers
• ISSN: 2509-9264; 2509-6656
• DOI: 10.1055/s-0043-119889

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.