Cytotoxic steroids from Monascus purpureus-fermented rice

Abstract Bioassay-guided fractionation of an EtOH extract of Monascus purpureus -fermented rice led to the isolation of two new steroids (22 S , 23 R , 24 S )-20 β ,23 α ,25 α -trihydroxy-16,22-epoxy-4,6,8(14)-trienergosta-3-one ( 1 ), the first example of a steroid possessing both a conjugated triene ketone system and a fused 4H-furan ring side chain within one molecule, and (22 E , 24 R )-3 β ,5 α -dihydroxyergosta-23-methyl-7,22-dien-6-one ( 2 ), as well as two known compounds (22 E , 24 R )-3 β ,5 α -dihydroxyergosta-7,22-dien-6-one ( 3 ) and (22 E , 24 R )-6 β -methoxy-ergosta-7,22-diene-3 β ,5 α -diol ( 4 ). Their structures were assigned by detailed interpretation of HRESIMS, 1D and 2D NMR spectroscopic data. The absolute stereochemistry of 1 was determined by single-crystal X-ray crystallography while the absolute stereochemistry of 2 was established by CD. Compounds 1 - 4 showed cytotoxic activity against the lung adenocarcinoma (A549) with IC 50 values of 0.08, 0.94, 12.6 and 13.5 μM, respectively. In addition, compounds 1 and 2 exhibited moderate activities against human ovarian cancer (A2780), with IC 50 values of 2.8 and 5.1 μM.