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Synthesis and Discovery of Estra-1,3,5(10),6,8-pentaene-2,16?-diol.

ABSTRACT: A metallacycle-centered approach to the assembly of partially aromatic synthetic steroids was investigated as a means to prepare a boutique collection of unique steroidal agents. The synthesis and discovery of estra-1,3,5(10),6,8-pentaene-2,16?-diol (VII) is described, along with structure-activity relationships related to its cytotoxic properties. Overall, VII was found to have a GI50 = 0.2 ?g/mL (?800 nM) in MDA-MB-231 human breast cancer cells, be an efficacious estrogen receptor agonist with potency for ER? > ER? (ER? EC50 = 21 nM), possess selective affinity to the cdc-2-like kinase CLK4 (Kd = 350 nM), and be phenotypically related to paclitaxel by an unbiased panel assessment.

SUBMITTER: Wai H

PROVIDER: S-EPMC6415968 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Synthesis and Discovery of Estra-1,3,5(10),6,8-pentaene-2,16α-diol.

Wai HtooTint H Du Kang K Anesini Jason J Kim Wan Shin WS Eastman Alan A Micalizio Glenn C GC

Organic letters 20180917 19

A metallacycle-centered approach to the assembly of partially aromatic synthetic steroids was investigated as a means to prepare a boutique collection of unique steroidal agents. The synthesis and discovery of estra-1,3,5(10),6,8-pentaene-2,16α-diol (VII) is described, along with structure-activity relationships related to its cytotoxic properties. Overall, VII was found to have a GI<sub>50</sub> = 0.2 μg/mL (∼800 nM) in MDA-MB-231 human breast cancer cells, be an efficacious estrogen receptor a ...[more]

PMID: 30221523

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