Anticancer (hexacarbonyldicobalt)propargyl aryl ethers: Synthesis, antiproliferative activity, apoptosis induction, and effect on cellular oxidative stress

Sydonie D. Schimler, David J. Hall, Stefan L. Debbert

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

While an increasing number of (hexacarbonyldicobalt)alkynes have been found to possess antiproliferative activity against a number of cancer cell lines, the role of the organometallic moiety in this bioactivity is not well understood. To gain a better understanding of cobalt's role in the medicinal chemistry of these compounds, several simplified analogs of a known organocobalt anticancer compound were synthesized and assessed for antiproliferative activity against MDA-MB-231 human breast cancer cells. These compounds, mostly (hexacarbonyldicobalt)propargyl aryl ethers, caused 45-93% growth inhibition of that cell line at 40 μM in a 72 h crystal violet staining assay. The most active analog was the organocobalt nitroaromatic ether 3a, with an IC 50 of 3.3 ± 0.9 μM. Flow cytometric assays on the same cell line demonstrated that 3a strongly induces apoptosis, arrests the cell cycle at the S phase, increases cellular oxidative stress levels, and induces permeability of the mitochondrial membrane. While the non-cobalt-containing precursor to 3a also caused an increase in mitochondrial membrane permeability, it did not produce an increase in oxidative stress levels, nor did it have apoptosis-inducing or antiproliferative effects. The induction of oxidative stress in the cell may be responsible for some of the antiproliferative activity of compound 3a against this cell line.

Original languageEnglish (US)
Pages (from-to)28-37
Number of pages10
JournalJournal of Inorganic Biochemistry
Volume119
DOIs
StatePublished - Feb 2013

Keywords

  • Organometallic medicinal chemistry
  • Oxidative stress

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