Addressing cytotoxicity of 1,4-biphenyl amide derivatives: Discovery of new potent and selective 17β-hydroxysteroid dehydrogenase type 2 inhibitors
| Autor: | Rolf W. Hartmann, Sandrine Marchais-Oberwinkler, Enrico Perspicace, Emanuele M. Gargano, Angelo Carotti |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Stereochemistry Cell Survival Clinical Biochemistry Pharmaceutical Science Dehydrogenase Biochemistry Estradiol Dehydrogenases 03 medical and health sciences chemistry.chemical_compound Structure-Activity Relationship Amide Drug Discovery Moiety Structure–activity relationship Humans Hydroxysteroid dehydrogenase Enzyme Inhibitors Cytotoxicity Molecular Biology Dose-Response Relationship Drug Molecular Structure Cytotoxins Organic Chemistry Biphenyl Compounds Amides Biphenyl compound 030104 developmental biology HEK293 Cells chemistry Molecular Medicine Lead compound |
| Zdroj: | Bioorganicmedicinal chemistry letters. 26(1) |
| ISSN: | 1464-3405 |
| Popis: | Four different classes of new 17β-hydroxysteroid dehydrogenase type 2 (17β-HSD2) inhibitors were synthesized, in order to lower the cytotoxicity exhibited by the lead compound A, via disrupting the linearity and the aromaticity of the biphenyl moiety. Compounds 3, 4, 7a and 8 displayed comparable or better inhibitory activity and selectivity, as well as a lower cytotoxic effect, compared to the reference compound A. The best compound 4 (IC50 = 160 nM, selectivity factor = 168, LD50 ≈ 25 μM) turned out as new lead compound for inhibition of 17β-HSD2. |
| Databáze: | OpenAIRE |
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