CJ-13, 981 and CJ-13, 982, New Squalene Synthase Inhibitors

Abstract

Two new squalene synthase (SSase) inhibitors, CJ-13, 981 (I) and CJ-13, 982 (II), were isolated from the fermentation broth of an unidentified fungus CL15036. They inhibited human liver microsomal SSase with IC₅₀s of 2.8 and 1.1 μM, respectively, but showed no inhibitory activity against human brain protein farnesyltransferase (PFTase) at 100 μM. Based on FAB-MS and NMR analyses, the structures of I and II were determined to be 3-hydroxy-3, 4-dicarboxy15-hexadecenoic acid and 3-hydroxy-3, 4-dicarboxyhexadecanoic acid, respectively.