ent-Labdane diterpenoid lactone stereoisomers from Andrographis paniculata

Two pairs of ent-labdane diterpenoid lactone stereoisomers (1- 4) including three new compounds (1- 3) were isolated from the 85% EtOH extract of the aerial parts of Andrographis paniculata. The structures of these compounds were identified as 7 R-hydroxy-14-deoxyandrographolide (1), 7 S-hydroxy-14-deoxyandrographolide (2), 12 S,13 S-hydroxyandrographolide (3), and 12 R,13 R-hydroxyandrographolide (4) by spectroscopic data analyses and calculated (13)C NMR data at the B3LYP/6-311++G(2d,p)//B3LYP/6-31G* level using the GIAO method. The 12 S-configuration of 4 was revised to 12 R based on the spectroscopic data. The antiproliferative activities of the two pairs of stereoisomers and 14 other ent-labdane diterpenoid derivatives were determined in human leukemia HL-60 cells. Andrographolide (7) and isoandrographolide (12) exhibited higher antiproliferative activities than other ent-labdane diterpenoids with GI 50's of 9.33 and 6.30 microM, respectively.