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Design, synthesis, and biological evaluation of conformationally constrained analogues of naphthol AS-E as inhibitors of CREB-mediated gene transcription.

ABSTRACT: Cyclic AMP response element binding protein (CREB) is often dysregulated in cancer cells and is an attractive cancer drug target. Previously, we described naphthol AS-E (1) as a small molecule inhibitor of CREB-mediated gene transcription. To understand its bioactive conformation, a series of conformationally constrained analogues of 1 were designed and synthesized. Biological evaluation of these analogues suggests that the global energy minimum of 1 is the likely bioactive conformation.

SUBMITTER: Jiang M

PROVIDER: S-EPMC3375358 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Design, synthesis, and biological evaluation of conformationally constrained analogues of naphthol AS-E as inhibitors of CREB-mediated gene transcription.

Jiang Min M Li Bingbing X BX Xie Fuchun F Delaney Frances F Xiao Xiangshu X

Journal of medicinal chemistry 20120409 8

Cyclic AMP response element binding protein (CREB) is often dysregulated in cancer cells and is an attractive cancer drug target. Previously, we described naphthol AS-E (1) as a small molecule inhibitor of CREB-mediated gene transcription. To understand its bioactive conformation, a series of conformationally constrained analogues of 1 were designed and synthesized. Biological evaluation of these analogues suggests that the global energy minimum of 1 is the likely bioactive conformation. ...[more]

PMID: 22458559

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