Cytotoxic steroids from Monascus purpureus-fermented rice

• Published in: Steroids 2011-09, Vol.76 (10), p.1185-1189
• Main Authors: Shang, Xiao-Ya, Li, Jin-Jie, Liu, Ming-Tao, Li, Shuai, Liu, Ying, Wang, Ye-Feng, Huang, Xiao, Jin, Zong-Lian
• Format: Article
• Language: English
• Subjects: Absolute configuration; Biological and medical sciences; Cell Line, Tumor; Cell Survival - drug effects; Crystallography, X-Ray; Cytotoxicity; Fermentation; Fundamental and applied biological sciences. Psychology; Humans; Magnetic Resonance Spectroscopy; Molecular Structure; Monascus - metabolism; Monascus purpureus; Oryza - chemistry; Oryza - microbiology; Steroids - chemistry; Steroids - pharmacology; Vertebrates: endocrinology; X-ray single crystal diffraction
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/j.steroids.2011.05.008

[Display omitted] ► Four steroids (compounds 1– 4) were isolated from Monascus purpureus-fermented rice. ► Compound 1 represents the first example of a steroid possessing both a conjugated triene ketone system and a fused 4 H-furan ring side chain within one molecule. ► The absolute configuration of 1 was determined by single-crystal X-ray. ► Compound 1 showed significant cytotoxic activity against the lung adenocarcinoma. 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.