Design, synthesis and biological evaluation of novel 3,4,5-trisubstituted aminothiophenes as inhibitors of p53-MDM2 interaction. Part 1
| Autor: | Weisi Wang, Lei Zhang, Yongzhou Hu, Chunqi Hu, Ni Qiu, Shihao Shangguan |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Clinical Biochemistry
Pharmaceutical Science Antineoplastic Agents Thiophenes Biochemistry Sensitivity and Specificity P53 mdm2 chemistry.chemical_compound Inhibitory Concentration 50 Structure-Activity Relationship Cell Line Tumor Drug Discovery P53 status Structure–activity relationship Humans Molecular Biology Biological evaluation Cell Proliferation Organic Chemistry Proto-Oncogene Proteins c-mdm2 Combinatorial chemistry Molecular Docking Simulation Kinetics chemistry Design synthesis Cell culture Drug Design Molecular Medicine Drug Screening Assays Antitumor Tumor Suppressor Protein p53 Selectivity Lead compound Protein Binding |
| Zdroj: | Bioorganicmedicinal chemistry. 21(11) |
| ISSN: | 1464-3391 |
| Popis: | A series of 3,4,5-trisubstituted aminothiophenes were designed, synthesized, and evaluated for their p53-MDM2 binding inhibitory potency and anti-proliferation activities against A549 and PC3 tumor cell lines. Fourteen compounds had appreciably improved MDM2 binding affinities than lead compound MCL0527 (3) and a few compounds showed comparable activities to that of Nutlin-3. Meanwhile, most of the 3,4,5-trisubstituted aminothiophenes displayed better or equivalent anti-proliferation activities against wild-type p53 cell line A549 compared to that of Nutlin-3. Over ten compounds exhibited desirable selective profiles of p53 status. Particularly, compounds 9, 16 and 18 displayed 22-, 6- and 22-fold selectivity of p53 status, respectively, much better than that of Nutlin-3 (fourfold). |
| Databáze: | OpenAIRE |
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