PMIO 2017; 4(03): e89-e92
DOI: 10.1055/s-0043-119889
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Antiproliferative Activity and Effect on GABAA Receptors of Callitrisic Acid Derivatives

Marco Stadler
1  Department of Pharmacology and Toxicology, University of Vienna, Vienna, Austria
,
José M. Padrón
2  BioLab, Instituto Universitario de Bio-Orgánica “Antonio González” (IUBO-AG), Centro de Investigaciones Biomédicas de Canarias (CIBICAN), Universidad de La Laguna, La Laguna, Tenerife, Spain
,
Miguel A. González-Cardenete
3  Instituto de Tecnología Química (UPV-CSIC), Universitat Politècnica de Valencia, Consejo Superior de Investigaciones Científicas, Valencia, Spain
› Author Affiliations
Further Information

Publication History

received 18 February 2017
revised 07 June 2017

accepted 08 September 2017

Publication Date:
18 October 2017 (online)

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 GABAA receptors (α 1 β 2 γ 2s) were evaluated. The GI50 values were in the range of 3.4–61 µM and the potentiation of IGABA 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 GABAA receptor modulating activities in the dehydroabietane scaffold has thus been revealed.