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2001•The Journal of AntibioticsOpen access

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

Shuzo Watanabe, Hideo Hirai, Takahito Kambara, Yasuhiro Kojima, HIROYUKI NLSHIDA, Ayumu Sugiura, Yuji Yamauchi, Nobuji Yoshikawa, H. James Harwood, Liang Huang, Nakao Kojima

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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 CL 15036. They inhibited human liver microsomal SSase with IC50s of 2.8 and 1.1 microM, respectively, but showed no inhibitory activity against human brain protein farnesyltransferase (PFTase) at 100 microM. Based on FAB-MS and NMR analyses, the structures of I and II were determined to be 3-hydroxy-3,4-dicarboxy-15-hexadecenoic acid and 3-hydroxy-3,4-dicarboxyhexadecanoic acid, respectively.

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What this paper is about

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 CL 15036. They inhibited human liver microsomal SSase with IC50s of 2.8 and 1.1 microM, respectively, but showed no inhibitory activity against human brain protein farnesyltransferase (PFTase) at 100 microM. Based on FAB-MS and NMR analyses, the structures of I and II were determined to be 3-hydroxy-3,4-dicarboxy-15-hexadecenoic acid and 3-hydroxy-3,4-dicarboxyhexadecanoic acid, respectively.

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Available 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 CL 15036. They inhibited human liver microsomal SSase with IC50s of 2.8 and 1.1 microM, respectively, but showed no inhibitory activity against human brain protein farnesyltransferase (PFTase) at 100 microM. Based on FAB-MS and NMR analyses, the structures of I and II were determined to be 3-hydroxy-3,4-dicarboxy-15-hexadecenoic acid and 3-hydroxy-3,4-dicarboxyhexadecanoic acid, respectively.

Key concepts: Squalene, Farnesyltransferase, Farnesyl-diphosphate farnesyltransferase, Microsome, Chemistry, ATP synthase, Fermentation, Biochemistry

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