Three New Cytotoxic ent-Kaurane Diterpenes from Isodon excisoides

Abstract

Three types of ent-kaurane diterpenoids were isolated from the aerial parts of Isodon excisoides, including three new diterpenoids, 1α,7α,14β-trihydroxy-20-acetoxy- ent-kaur-15-one ( 1); 1α,7α,14β,18-tetrahydroxy-20-acetoxy- ent-kaur-15-one ( 2); and 1α-acetoxy-14β-hydroxy-7α,20-epoxy- ent-kaur-16-en-15-one ( 3); together with six known diterpenes henryin ( 4); kamebanin ( 5); reniformin C ( 6); kamebacetal A ( 7); kamebacetal B ( 8); and oridonin ( 9). The structures of the isolated compounds were elucidated by means of nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry in conjunction with published data for their analogs, as well as their fragmentation patterns. Compounds 5 and 9 were isolated from Isodon excisoides for the first time. To explore the structure-activity relationships of the isolated compounds, they were tested for their cytotoxic effects against five human cancer cell lines: HCT-116, HepG2, A2780, NCI-H1650, and BGC-823. Most of the isolated compounds showed certain cytotoxic activity against the five cancer cell lines with IC ₅₀ values ranging from 1.09–8.53 µM. Among the tested compounds, compound 4 exhibited the strongest cytotoxic activity in the tested cell lines, with IC ₅₀ values ranging from 1.31–2.07 µM. Compounds 1, 6, and 7 exhibited selective cytotoxic activity.