Synthesis and Discovery of Estra-1,3,5(10),6,8-pentaene-2,16α-diol
dataset
posted on 2018-09-14, 20:16 authored by HtooTint Wai, Kang Du, Jason Anesini, Wan Shin Kim, Alan Eastman, Glenn C. MicalizioA 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 (<b>VII</b>) is described, along with structure–activity relationships
related to its cytotoxic properties. Overall, <b>VII</b> 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 agonist with potency for ERβ > ERα (ERβ
EC<sub>50</sub> = 21 nM), possess selective affinity to the cdc-2-like
kinase CLK4 (K<sub>d</sub> = 350 nM), and be phenotypically related
to paclitaxel by an unbiased panel assessment.
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