Cytotoxic Lathyrane-Type Diterpenes from Seeds of Euphorbia lathyris

Abstract

We isolated two new lathyrane-type diterpenes L₂₇ (1) and L₂₈ (2) along with seven known compounds (3–9) from the seeds of Euphorbia lathyris. These compounds were identified by NMR, high-resolution electrospray ionisation (HR-ESI)-MS as well as IR spectroscopy. Compounds 1 and 2 were assigned NMR spectrums with ¹H-NMR, ¹³C-NMR, distortionless enhancement by polarization (DEPT), correlation spectroscopy (COSY), heteronuclear multiple quantum coherence (HMQC), heteronuclear multiple bond connectivity (HMBC) and nuclear Overhauser effect spectroscopy (NOESY). Stereo configuration of 1 and 2 were confirmed by comprehensive interpretation of their nuclear Overhauser effect (NOE) relationship and showed they were first natural lathyrane-type diterpenes possessing α-configuration substitutes at C-3. Cytotoxicity assay of isolated compounds were evaluated against breast cancer cell lines MCF-7 or MDA-MB-231, 786-0 and liver cancer cell lines HepG2. As a result, Euphorbia factor L₂₈ (2) showed strongly cytotoxicity to the 786-0 and HepG2 cell lines, with an IC₅₀ value of 9.43 and 13.22 µM, respectively, which preliminarily suggested that the configuration of lathyrane-type diterpene at C-3 has a significant effect on its bioactivity.

Graphical Abstract