ABSTRACT
Bioassay-guided fractionation of an EtOH extract of Monascus purpureus-fermented rice led to the isolation of two new steroids (22S, 23R, 24S)-20ß,23α,25α-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 (22E, 24R)-3ß,5α-dihydroxyergosta-23-methyl-7,22-dien-6-one (2), as well as two known compounds (22E, 24R)-3ß,5α-dihydroxyergosta-7,22-dien-6-one (3) and (22E, 24R)-6ß-methoxy-ergosta-7,22-diene-3ß,5α-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.
Subject(s)
Monascus/metabolism , Oryza/chemistry , Steroids/chemistry , Steroids/pharmacology , Cell Line, Tumor , Cell Survival/drug effects , Crystallography, X-Ray , Fermentation , Humans , Magnetic Resonance Spectroscopy , Molecular Structure , Oryza/microbiologyABSTRACT
One unusual aromatic monacolin analog, monacophenyl, was isolated from the ethanolic extract of Monascus purpureus-fermented rice. Its structure was completely and unambiguously assigned by one- and two-dimensional NMR techniques ((1)H NMR, (13)C NMR, HSQC, HMBC and NOESY) and high-resolution ESI-MS spectrometry.
Subject(s)
Lovastatin/chemistry , Monascus/chemistry , Oryza/chemistry , Pyrones/chemistry , Tetrahydronaphthalenes/chemistry , Anticholesteremic Agents/chemistry , Lovastatin/analogs & derivatives , Magnetic Resonance Spectroscopy , Molecular StructureABSTRACT
Using a cell-based cytotoxicity assay three new cytotoxic azaphilones, including two stereoisomers and designated monapurones A-C (1-3), were isolated from the extract of Monascus purpureus-fermented rice (red yeast rice). Their structures were elucidated by detailed interpretation of spectroscopic and chemical data. The relative configurations were assigned on the basis of analysis of NOE data, and the absolute configurations were determined by direct comparison of their CD spectra with those of known azaphilones and chemical correlations. In the in vitro assays, monapurones A-C (1-3) showed selective cytotoxicity against human cancer cell line A549 with IC50 values of 3.8, 2.8 and 2.4 microM respectively, while exhibiting no significant toxicity to normal MRC-5 and WI-38 cells at the same concentration.
