Ternifolipyrons A–J: new cytotoxic α-pyrones from Isodon ternifolius (D. Don) Kudô

Abstract

Isodon ternifolius (D.Don) Kudô is an important Asian herb used in traditional medicine against several diseases. Nineteen compounds were isolated from the dichloromethane–methanol (1 : 1) extract of I. ternifolius roots, including ten new α-pyrone derivatives, named ternifolipyrons A–J. The chemical structures of the isolates were determined by a combination of 1D and 2D NMR, along with LR- and HRMS spectroscopy. The absolute configurations of the α-pyrone derivatives were constructed based upon the X-ray signal crystal of the bromobenzoyl derivative of 1 as well as the electronic circular dichroism (ECD). All isolates (1–19) were investigated for their growth-inhibitory potential towards CCRF-CEM-leukemia cells at a fixed concentration of 30 μM. The compounds which exerted more than 50% inhibition at this concentration, compounds (7, 10, 12, 15–17), were tested at a different concentration range to determine their IC₅₀ values in CCRF-CEM leukemia, MDA-MB-231 triple-negative breast cancer, and MCF7 breast cancer cell lines. Ursolic acid (16) showed the most potent activity against the three cancer cell lines with IC₅₀ values of 8.37, 18.04, and 18.93 μM, respectively.