Glioblastoma multiforme (GBM) is the worst form of
primary brain tumor, which has a high rate of infiltration and resistance to radiation and
chemotherapy, resulting in poor prognosis for patients. Recent studies show that thiazolidinones have a wide range of pharmacological properties including antimicrobial, anti-inflammatory,
anti-oxidant and anti-
tumor. Here, we investigate the effect antiglioma in vitro of a panel of sixteen synthetic 2-aryl-3-((piperidin-1-yl)ethyl)thiazolidin-4-ones where 13 of these decreased the viability of
glioma cells 30-65% (100 μM) compared with controls. The most promising compounds such as 4d, 4l, 4m and 4p promoted
glioma reduction of viability greater than 50%, were further tested at lower concentrations (12.5, 25, 50 and 100 μM). Also, the data showed that the compounds 4d, 4l, 4m and 4p induced cell death primarily through
necrosis and late apoptosis mechanisms. Interestingly, none of these 2-aryl-3-((piperidin-1-yl)ethyl)thiazolidin-4-ones were cytotoxic for primary astrocytes, which were used as a non-transformed cell model, indicating selectivity. Our results also show that the treatment with sub-therapeutic doses of 2-aryl-3-((piperidin-1-yl)ethyl)thiazolidin-4-ones (4d, 4l and 4p) reduced in vivo
glioma growth as well as malignant characteristics of implanted
tumors such as intratumoral
hemorrhage and peripheral pseudopalisading. Importantly, 2-aryl-3-((piperidin-1-yl)ethyl)thiazolidin-4-ones treatment did not induce mortality or peripheral damage to animals. Finally, 2-aryl-3-((piperidin-1-yl)ethyl)thiazolidin-4-ones also changed the
nitric oxide metabolism which may be associated with reduced growth and malignity characteristics of
gliomas. These data indicates for the first time the therapeutic potential of synthetic 2-aryl-3-((piperidin-1-yl)ethyl)thiazolidin-4-ones to GBM treatment.