Abstract
Thiazolidinone compounds 1-3 are lead compounds that have cytoselective toxicity toward non-small cell lung cancer (NSCLC) cells and drug-resistant NSCLC cells while showing low toxicity to normal human fibroblasts (NHFB). However, this class of compounds generally has a very low aqueous solubility (∼0.1 μg/ml). In order to improve both solubility and anti-cancer activity, we designed and synthesized two lead-optimization libraries and investigated these libraries using simultaneous high-throughput solubility and cytotoxicity assays. By all-around modifications on R1, R2 and R3 substitutions, consecutive library synthesis, and testing, we improved the aqueous solubility (5-fold improvement in solubility, from 0.1 to 0.5 μg/ml) and anti-cancer activity (10-fold improvement in EC50 from 0.72-0.98 μM to 0.08-0.16 μM) in the new lead thiazolidinone compound 31.
Original language | English (US) |
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Pages (from-to) | 1971-1975 |
Number of pages | 5 |
Journal | Bioorganic and Medicinal Chemistry Letters |
Volume | 25 |
Issue number | 9 |
DOIs | |
State | Published - May 1 2015 |
Externally published | Yes |
All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry