Cytotoxic sesquiterpenes from Ligularia platyglossa

Abstract

Four sesquiterpene lactones including an eremophilenolide dimer, named as biligulaplenolide, <b>1</b>, 8β-hydroxy-1-oxo-(14α,15α eremophil-7(11),9(10)-dien-12,8α-olide, <b>2</b>, 1-hydroxy-2-oxo-(14α,15α eremophil-1(10),7(11),8(9)-trien-12,8-olide, <b>3</b>, 4α,8β,9α-trihydroxy- 5αΗ-7(11)-eudesmen-12,8α-olide, <b>4</b>, along with two known ones, 10α-hydroxy-1-oxo-eremophil-7(11),8(9)-dien-12,8-olide, <b>5</b>, and furanoeremophil-1(10)-ene-2,9-dione, <b>6</b>, were isolated from the underground organs of <i>Ligularia platyglossa</i> (Franch.) Hand.-Mazz. Their structures were elucidated by spectroscopic methods including single-crystal X-ray diffraction analysis (<b>2</b> and <b>3</b>). Their <i>in vitro</i> cytotoxicities against seven cancer cell lines (BGC-823, A549, HL-60, B16, SMMC-7721, BEL7402, Hela) were evaluated. Compounds <b>2</b>, <b>3</b>, <b>5</b> showed cytotoxic activities on HL-60 cancer cells with IC₅₀ in the range of 24.0 to 51.1 μM, whereas compound <b>3</b> exhibited only weak cytotoxic activity against the B16, BEL7402 and Hela cancer cells. Flow cytometric analysis indicated that compound <b>3</b> induces Hela cells to apoptotic death after 48 h treatment with 0.38 mM of this compound.