Study of novel anticancer 4-thiazolidinone derivatives

Chem Biol Interact. 2017 Jan 25:262:46-56. doi: 10.1016/j.cbi.2016.12.008. Epub 2016 Dec 11.

Abstract

4-Thiazolidinones are a known class of prospective drug-like molecules, especially in the design of new anticancer agents. Two of the most prominent subtypes of these compounds are 5-ene-2-amino(amino)-4-thiazolidinones and thiopyrano[2,3-d]thiazoles. The latter are considered to be cyclic mimetics of biologically active 5-ene-4-thiazolidinones with similar pharmacological profiles. Therefore, the aim of this study was to evaluate the impact of 4-thiazolidinone-based compounds on cytotoxicity, the apoptotic process, and metabolism in the human squamous carcinoma (SCC-15) cell line. The SCC-15 cells were cultured in phenol red-free DMEM/F12 medium supplemented with 10% FBS, hydrocortisone, and exposed to rising concentrations (1 nM-100 μM) of the studied compounds for 6, 24 and 48 h. Afterwards, reactive oxygen species (ROS) formation, cell viability, caspase-3 activity, and cell metabolism were measured. The obtained results showed that all of the studied compounds in a wide range of concentrations (1 nM-100 μM) increased DCF fluorescence which suggests a stimulation of ROS production. Nevertheless, these new compounds showed cytotoxic and proapoptotic properties only at high (10-100 μM) concentrations. Our studies are the first to be carried out on these compounds and require further investigation to clarify the mechanism of action of their anticancer potential.

Keywords: Anticancer activity; Apoptosis; Cytotoxicity; Thiazolidinone; Thiazolothiopyranes.

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Humans
  • L-Lactate Dehydrogenase / metabolism
  • Microscopy, Fluorescence
  • Reactive Oxygen Species / metabolism
  • Thiazoles / chemistry
  • Thiazoles / pharmacology*

Substances

  • Antineoplastic Agents
  • Reactive Oxygen Species
  • Thiazoles
  • L-Lactate Dehydrogenase
  • Caspase 3