Design, Synthesis, Activity and Docking Study of Sorafenib Analogs Bearing Sulfonylurea Unit
| Autor: | Min Wang, Wufu Zhu, Le Chen, Chunjiang Wu, Qidong Tang, Rong Luo, Pengwu Zheng |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Niacinamide
Stereochemistry medicine.drug_class Pharmaceutical Science sulfonylurea Antineoplastic Agents VEGFR2/KDR kinase inhibitors Protein Structure Secondary Article Analytical Chemistry HeLa lcsh:QD241-441 Inhibitory Concentration 50 Structure-Activity Relationship chemistry.chemical_compound lcsh:Organic chemistry Cell Line Tumor Drug Discovery medicine Humans Structure–activity relationship Physical and Theoretical Chemistry Cytotoxicity Binding Sites biology Phenylurea Compounds Aryl Organic Chemistry Hydrogen Bonding biology.organism_classification Vascular Endothelial Growth Factor Receptor-2 Sulfonylurea Protein Structure Tertiary Molecular Docking Simulation Sulfonylurea Compounds anticancer activity chemistry Chemistry (miscellaneous) Docking (molecular) Drug Design Urea Molecular Medicine sorafenib Drug Screening Assays Antitumor |
| Zdroj: | Molecules, Vol 20, Iss 10, Pp 19361-19371 (2015) Molecules Volume 20 Issue 10 Pages 19361-19371 |
| ISSN: | 1420-3049 |
| Popis: | Two series of novel sorafenib analogs containing a sulfonylurea unit were synthesized and their chemical structures were confirmed by 1H-NMR, 13C-NMR, MS spectrum and elemental analysis. The synthesized compounds were evaluated for the cytotoxicity against A549, Hela, MCF-7, and PC-3 cancer cell lines. Some of the compounds showed moderate cytotoxic activity, especially compounds 1-(2,4-difluorophenylsulfonyl)-3-(4-(2-(methylcarbamoyl)pyridin-4-yloxy)phenyl)urea (6c) and 1-(4-bromophenylsulfonyl)-3-(4-(2-(methylcarbamoyl)pyridin-4-yloxy)phenyl)urea (6f) with the IC50 values against four cancer cell lines ranging from 16.54 ± 1.22 to 63.92 ± 1.81 μM, respectively. Inhibitory rates against vascular endothelial growth factor receptor-2 (VEGFR2/KDR) kinase at 10 μM of target compounds were further carried out in this paper in order to investigate the target of these compounds. Structure-activity relationships (SARs) and docking studies indicated that the sulfonylurea unit was important to these kinds of compounds. None of the substitutions in the phenoxy group and small halogen atoms such as 2,4-difluoro substitution of the aryl group contributed to the activity. The results suggested that sulfonylurea sorafenib analogs are worthy of further study. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|