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

Journal Article · Sun Dec 15 04:00:00 EST 2019 · Medicinal Chemistry Research (Print)

DOI:https://doi.org/10.1007/S00044-019-02444-Z· OSTI ID:22936153

Saralkar, Pushkar

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 IC{sub 50} of 7.1 μM, whereas its unsaturated derivative CI-987 was more potent with a IC{sub 50} 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.

• OSTI ID: 22936153
• Journal Information: Medicinal Chemistry Research (Print), Journal Name: Medicinal Chemistry Research (Print) Journal Issue: 12 Vol. 28; ISSN 1054-2523
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AROMATICS
BRAIN
CELL PROLIFERATION
DRUGS
GALACTOSE
GLYCOLYSIS
MAMMARY GLANDS
MITOCHONDRIA
NEOPLASMS