Euphorane C, an unusual C17-norabietane diterpenoid from Euphorbia dracunculoides induces cell cycle arrest and apoptosis in human leukemia K562 cells

Abstract

Four new polycyclic diterpenoids euphoranes A − D ( 1 – 4 ), together with 12 known terpenoids ( 5 – 16 ) were isolated from the whole plants of Euphorbia dracunculoides . Compound 2 represents the first example of aromatic 15,16,17-trinorabietane diterpenoid in Euphorbia species, and euphorane C ( 3 ) is an unusual 17-norabietane diterpenoid. The absolute configurations of 1 , 2 , and 4 were determined by single crystal X-ray diffraction, while that of 3 was established with the aid of ECD and 1D NMR quantum chemical calculation. Moreover, the absolute stereochemistry of 11 was demonstrated for the first time by crystallographic data. Compounds 1 – 16 were screened for antiproliferative activities against five human cancer cell lines, and 3 showed significant cytotoxicity against the human leukemia K562 cells with IC 50 value of 3.59 μM. Preliminary mechanistic investigation revealed that 3 could induce cell cycle arrest at G0/G1 phase and apoptosis in K562 cells.