Biological activities of novel zaragozic acids, the potent inhibitors of squalene synthase, produced by the fungus, Mollisia sp. SANK 10294.
Four novel zaragozic acids, F-10863A, B, C and D, were isolated from a culture broth of the fungus Mollisia sp. SANK 10294. F-10863 compounds contain a 4,6,7-trihydroxy-2,8-dioxyobicyclo-[3.2.1]octane-3,4,5-tricarboxyl ic acid core like previously reported zaragozic acids, but the structures of the side chains are different. Recently, it was found that F-10863A is identical to zaragozic acid D3, while the other three are novel compounds. F-10863 compounds are potent inhibitors of squalene synthase like previously reported zaragozic acids, and, furthermore, they exhibit serum cholesterol-lowering activity in vivo.
Tanimoto
T
T
Pharmacology and Molecular Biology Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
Hamano
K
K
Onodera
K
K
Hosoya
T
T
Kakusaka
M
M
Hirayama
T
T
Shimada
Y
Y
Koga
T
T
Tsujita
Y
Y
D000818:Animals; D000924:Anticholesteremic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001203:Ascomycota; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000302:isolation & purification / Q000494:pharmacology*; D002144:Callithrix; D002417:Cattle; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood; D006224:Cricetinae; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D008297:Male; D008647:Mesocricetus; D051379:Mice; D051381:Rats
D000924:Anticholesteremic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004791:Enzyme Inhibitors; D002784:Cholesterol; D013186:Farnesyl-Diphosphate Farnesyltransferase