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RESEARCH PRODUCT

Study of novel anticancer 4-thiazolidinone derivatives

Konrad A. SzychowskiO. R. PinyazhkoDanylo KaminskyyMarcin L. LejaRoman LesykUrszula E. BindugaJan Gmiński

subject

0301 basic medicineCell SurvivalCytotoxicityAntineoplastic AgentsApoptosisToxicology01 natural sciencesAnticancer activity03 medical and health sciencesCell Line TumormedicineHumansViability assayCytotoxicitychemistry.chemical_classificationReactive oxygen speciesL-Lactate Dehydrogenase010405 organic chemistryChemistryCaspase 3ThiazolothiopyranesBiological activityGeneral MedicineMetabolism0104 chemical sciencesSquamous carcinomaThiazoles030104 developmental biologyMechanism of actionBiochemistryMicroscopy FluorescenceCell cultureThiazolidinonemedicine.symptomReactive Oxygen Species

description

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.

10.1016/j.cbi.2016.12.008https://doi.org/10.1016/j.cbi.2016.12.008