Structure, Absolute Configuration, and Antiproliferative Activity of Abietane and Icetexane Diterpenoids from Salvia...

From the aerial parts of Salvia ballotiflora, eleven diterpenoids were isolated; among them, four icetexanes and one abietane (1-5) are reported for the first time. Their structures were established by spectroscopic means, mainly ¹H- and ¹³C-NMR, including 1D and 2D homo- and hetero-nuclear experiments. Most of the isolated diterpenoids were tested for their antiproliferative, anti-inflammatory, and radical scavenging activities using the sulforhodamine B assay on six cancer cell lines, the TPA-induced ear edema test in mice, and the reduction of the DPPH assay, respectively. Some diterpenoids showed anti-proliferative activity, these being icetexanes 6 and 3, which were the most active with IC₅₀ (μM) = 0.27 ± 0.08 and 1.40 ± 0.03, respectively, for U251 (human glioblastoma) and IC₅₀ (μM) = 0.0.46 ± 0.05 and 0.82 ± 0.06 for SKLU-1 (human lung adenocarcinoma), when compared with adriamycin (IC₅₀ (μM) = 0.08 ± 0.003 and 0.05 ± 0.003, as the positive control), respectively. Compounds 3 and 10 showed significant reduction of the induced ear edema of 37.4 ± 2.8 and 25.4 ± 3.0% (at 1.0 μmol/ear), respectively. Compound 4 was the sole active diterpenoid in the antioxidant assay (IC₅₀ = 98. 4 ± 3.3), using α-tocopherol as the positive control (IC₅₀ (μM) = 31.7 ± 1.04). The diterpenoid profile found is of chemotaxonomic relevance and reinforces the evolutionary link of S. ballotiflora with other members of the section Tomentellae.