11,12-seco-Abietane-type diterpene lactones with potential antiplatelet activity from Salvia prattii

Abstract

Eleven new abietane-type diterpene lactones, salpratlactones D–N (1–11), including five 11,12-seco-11-nor-abietane diterpenes (1–5), four 11,12-seco-abietane diterpenes (6–9), two 20(10 → 5)-abeo-4,5;11,12-bis-seco-abietane diterpenes (10–11), and two known analogues (12–13), were characterized from Salvia prattii. Notably, compounds 1–3 were characterized by a unique linear 6/6/6 tricyclic skeleton. The structures were established by spectroscopic data interpretation, calculated NMR-DP4+ and electronic circular dichroism analysis, as well as single-crystal X-ray diffraction. A bioactivity study showed that 1, 2, 5, 11, and 12 can potently inhibit platelet aggregation induced by arachidonic acid (AA), with IC50 values of 5.66–16.10 μg/ml, stronger than aspirin. In addition, the lactate dehydrogenase assay showed that they had no effect on platelet integrity. Structurally, the same 1,2-benzopyrone fragments of 1, 2, and 5 should be the important pharmacophore for antiplatelet activity.