Two New Anti‐Proliferative C18‐Norditerpenes from the Roots of Podocarpus macrophyllus

Activity‐guided fractionation strategy was used to investigate chemical constituents from the roots of Podocarpus macrophyllus. Successfully, two new norditerpenes, 2β‐hydroxymakilactone A ( 1 ) and 3β‐hydroxymakilactone A ( 2 ), along with ten known analogues ( 3  –  12 ) were isolated. The structures of 1 and 2 were elucidated by spectroscopic analysis including 1D‐, 2D‐NMR, and HR‐ESI‐MS data. The previously reported structure of 2,3‐dihydro‐2α‐hydroxypodolide was revised as 2,3‐dihydro‐2β‐hydroxypodolide ( 3 ) by spectroscopic analysis, and was further confirmed by X‐ray crystallographic analysis. Cytotoxic activities of all isolated compounds against five human solid tumour cell lines (AGS, HeLa, MDA‐MB‐231, HepG‐2, and PANC‐1) were evaluated. All of them exhibited anti‐proliferative activities (IC₅₀ = 0.3 – 27 μm ), except for 10 . Compounds 1 , 4 , 5 , 6 , and 8 exhibited potent inhibitory activities with IC₅₀ < 1 μm against HeLa and AGS cells.