Anti-cancer Leading Compounds Thiazolidinone:Structure Optimization And Cytoselection

The developments of combinatorial chemistry, parallel synthesis, analysis, automatic purification, and high throughput screening techniques have been greatly improved in the past decades. The application of combinatorial chemistry has been widely applied in the discovery and optimization of lead compounds. This study is committed to the development of new anti-cancer drugs, which can kill both the drug-sensitive lung cancer cells H460and paclitaxel-resistant lung cancer cells H460/TaxR, But do not show toxicity towards normal human fibroblast (NHFB). Through the optimization of the drug, we improve the water-solubility and permeability, thus improving their anti-cancer activity.Lung cancer is the number one cause of cancer-related deaths worldwide. More than80%of bronchogenic malignancy is from non-small cell lung cancer (NSCLC). However the bottleneck to the development of effective anticancer drugs does not lie on an inability to identify chemicals that will kill cancer cells. Instead, the bottleneck lies on our inability to identify chemicals that will kill cancer cells at concentrations that do not harm patients. On the other hand, currently available therapies have been only temporarily successful for most cancer patients because they frequently lead to resistance. Thus, resistance to treatment and dose-limiting toxicity are two primary reasons for the failure of anticancer therapies. Resistance to treatment may arise through multidrug resistance(MDR), which is a phenotype of cross-resistance to multiple drugs. One mechanism underpinning MDR is the overexpression of the MDR-1gene that encodes the transmembrane, ATP-dependent, drug efflux transporter P-gp in response to chemotherapy. Therefore, it’s an important step for the Success of cancer therapy to discover new compounds that are not substrates of P-gp and are affective against both drug-sensitive and drug-resistant cancer cells but spare normal human cells.Two thiazolidinone derivatives have been identified to inhibit the growth of Paclitaxel-sensitive and-resistant NSCLC cell lines H460and H460/TaxR. Both of them showed relatively low toxicity toward NHFB. But the poor solubility (less than0.1μg/ml in DMSO) limits their biological activity. This study design a new thiazolidinone derivatives library based on the former library and the structure-activity relationship, which can keep the activity as the former compounds, at the same time we use the hydrophilic groups of R2and introducing R3groups to improve the solubility and we achieved a good effect. We also found a few compounds with good solubility and anti-cancer activity. This can make the thiazolidinone compounds powerful anti-cancer weapons and provide the solid guarantee to be a drug.