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Medicinal Chemistry Research

, Volume 28, Issue 12, pp 2165–2170 | Cite as

Screening for anticancer properties of thiazolidinedione compounds in a galactose media metastatic breast cancer cell model

  • Pushkar Saralkar
  • Werner J. GeldenhuysEmail author
Original Research
  • 47 Downloads

Abstract

The metastatic tumors of breast cancer lead to the mortality of patients in part due to the failure of chemotherapeutics to reach the brain and emergence of drug resistance. With the increase in drug resistance, we focused on targeting mitochondrial metabolism, which was recently found to be a viable and novel drug target in breast cancer. Here we screened several ligands for anticancer activity in a phenotypic screen using the MTT dye as a marker for cell proliferation. MCF-7 breast cancer cells were treated with compounds in the presence of galactose to ensure mitochondrial interaction by the compounds. The lead compound of our group, NL-1, a thiazolidinedione (TZD), was found to inhibit cell proliferation with an IC50 of 7.1 μM, whereas its unsaturated derivative CI-987 was more potent with a IC50 of 3.3 μM. The TZDs were affected by substitution on both the aromatic ring and the TZD warhead. Taken together, these compounds can serve as lead structures for mitochondrial targeted drug discovery programs in breast cancer.

Keywords

Warburg Mitochondria Glycolysis Cisd1 Cisd2 Phenotypic screen 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Pharmaceutical Sciences, School of PharmacyWest Virginia UniversityMorgantownUSA

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