Cytotoxic dehydromonacolins from red yeast rice.
Two new dehydromonacolins (1 and 3), together with nine known monacolins (4-12), were isolated from red yeast rice. Compounds 4-6 were isolated from a natural resource for the first time. Their structures were elucidated by means of NMR and mass spectroscopic analyses. The structure of dehydromonacolin N (1) was further confirmed by its semisynthesis from monacolin K (lovastatin) (11). Dehydromonacolin J (2), an intermediate in the semisynthesis of 1, was obtained as a new dehydromonacolin. The structure of dehydromonacolin L (3) was also confirmed by an elimination reaction of monacolin L (12). Compound 1, possessing a C2 side chain, is unprecedented in the natural monacolin family and exhibited moderate cytotoxic activity against Hep G2, Caco-2, and MCF-7 cancer cell lines. Dehydromonacolin K (8) demonstrated the most potent cytotoxicity to all three of these cell lines. The structure-activity relationship of natural and synthesized monacolins was discussed. This is the first report on the cytotoxic effects of dehydromonacolins.
School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, People's Republic of China.
Lin
L
Zhu
Lee-Fong
LF
Yau
Jing-Guang
JG
Lu
Guo-Yuan
GY
Zhu
Jing-Rong
JR
Wang
Quan-Bin
QB
Han
Wen-Luan
WL
Hsiao
Zhi-Hong
ZH
Jiang
D000970:Antineoplastic Agents; D001688:Biological Products / Q000737:chemistry*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008148:Lovastatin / Q000032:analysis / Q000737:chemistry; D032741:Monascus; D009281:Naphthalenes / Q000032:analysis* / Q000737:chemistry; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D001688:Biological Products; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009281:Naphthalenes; C477971:monacolin N; C117343:red yeast rice; C045375:monacolin L; D008148:Lovastatin; C045376:monacolin J