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Surprising unreactivity of cholesterol-5,6-epoxides towards nucleophiles.

ABSTRACT: We recently established that drugs used for the treatment and the prophylaxis of breast cancers, such as tamoxifen, were potent inhibitors of cholesterol-5,6-epoxide hydrolase (ChEH), which led to the accumulation of 5,6?-epoxy-cholesterol (5,6?-EC) and 5,6?-epoxy-cholesterol (5,6?-EC). This could be considered a paradox because epoxides are known as alkylating agents with putative carcinogenic properties. We report here that, as opposed to the carcinogen styrene-oxide, neither of the ECs reacted spontaneously with nucleophiles. Under catalytic conditions, 5,6?-EC remains unreactive whereas 5,6?-EC gives cholestan-3?,5?-diol-6?-substituted compounds. These data showed that 5,6-ECs are stable epoxides and unreactive toward nucleophiles in the absence of a catalyst, which contrasts with the well-known reactivity of aromatic and aliphatic epoxides. These data rule out 5,6-EC acting as spontaneous alkylating agents. In addition, these data support the existence of a stereoselective metabolism of 5,6?-EC.

SUBMITTER: Paillasse MR

PROVIDER: S-EPMC3307648 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Surprising unreactivity of cholesterol-5,6-epoxides towards nucleophiles.

Paillasse Michael R MR Saffon Nathalie N Gornitzka Heinz H Silvente-Poirot Sandrine S Poirot Marc M de Medina Philippe P

Journal of lipid research 20120129 4

We recently established that drugs used for the treatment and the prophylaxis of breast cancers, such as tamoxifen, were potent inhibitors of cholesterol-5,6-epoxide hydrolase (ChEH), which led to the accumulation of 5,6α-epoxy-cholesterol (5,6α-EC) and 5,6β-epoxy-cholesterol (5,6β-EC). This could be considered a paradox because epoxides are known as alkylating agents with putative carcinogenic properties. We report here that, as opposed to the carcinogen styrene-oxide, neither of the ECs reacte ...[more]

PMID: 22285872

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Dataset Information

Surprising unreactivity of cholesterol-5,6-epoxides towards nucleophiles.

Publications

Surprising unreactivity of cholesterol-5,6-epoxides towards nucleophiles.

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