Cytotoxic and Anti-Inflammatory Activity of Labdane and cis-Clerodane Type Diterpenes

Two labdane type diterpenes, labd-13( E )-ene,-8α,15-diol ( 1 ) and labd-13( E )-ene,-8α,15-yl acetate ( 2 ) were isolated from the hexane extract of Cistus creticus subsp. eriocephalus (Viv.) Greuter & Burdet leaves, while (+)-19-acetoxy- cis -clerodan-3-en-15-oic acid ( 3 ) was isolated from the hexane extract of Cistus monspeliensis L. leaves. The compounds were examined for their in vitro cytostatic and cytotoxic activity against nine human leukemic cell lines, three of which exhibited a multidrug resistant phenotype. They were also evaluated for their anti-inflammatory activity in vivo on the back of hairless mice. The cytostatic and cytotoxic activity of the tested diterpenes followed the order 1 > 2 > 3 . Topical application of the diterpenes on barrier disrupted skin did not seem to have a significant contribution to the repair rate of the skin barrier. Abbreviations GI 50 :growth inhibition 50 LC 50 :lethal concentration 50 MED:minimum erythymal dose MDR:multidrug resistant MTT:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide PBS:phosphate buffered saline RI:retention indices R t :retention time TEWL:transepidermal water loss TGI:total growth inhibition