Modulating the Cyclic Guanosine Monophosphate Substrate Selectivity of the Phosphodiesterase 3 Inhibitors by Pyridine, Pyrido[2,3-d]pyrimidine Derivatives and Their Effects upon the Growth of HT-29 Cancer Cell Line
| العنوان: | Modulating the Cyclic Guanosine Monophosphate Substrate Selectivity of the Phosphodiesterase 3 Inhibitors by Pyridine, Pyrido[2,3-d]pyrimidine Derivatives and Their Effects upon the Growth of HT-29 Cancer Cell Line |
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| المؤلفون: | Gary A. Piazza, Marwa Saeed Hany, Bernard D. Gary, Heather N. Tinsley, Ashraf H. Abadi, Amal Abdel Haleem Eissa, Shimaa Awadain Elsharif |
| المصدر: | Chemical and Pharmaceutical Bulletin. 61:405-410 |
| بيانات النشر: | Pharmaceutical Society of Japan, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Formamide, Pyrimidine, Pyridines, Stereochemistry, Phosphodiesterase 3, Phosphodiesterase 3 Inhibitors, Article, Substrate Specificity, Structure-Activity Relationship, chemistry.chemical_compound, Hydrolysis, Catalytic Domain, Drug Discovery, Pyridine, Humans, Cyclic GMP, Cyclic guanosine monophosphate, Cell Proliferation, Binding Sites, Chemistry, General Chemistry, General Medicine, Cyclic Nucleotide Phosphodiesterases, Type 3, Molecular Docking Simulation, Pyrimidines, Cyclization, Amine gas treating, Selectivity, HT29 Cells, Protein Binding |
| الوصف: | Analogues with the scaffolds of 3-cyano-4-alkoxyphenyl-6-bromoaryl-2-pyridone and 2-amino-3-cyano-4-alkoxyphenyl-6-bromoarylpyridine were synthesized. Cyclization of the 2-amino derivatives with formic acid and formamide gave the corresponding pyrido[2,3-d]pyrimidin-4(3H)-one and the pyrido[2,3-d]-pyrimidin-4-amine derivatives, respectively. Active phosphodiesterase 3 (PDE3) inhibitors were identified from each of the four aforementioned scaffolds. This is the first report that pyrido[2,3-d]pyrimidin-4(3H)-one and pyrido[2,3-d]pyrimidin-4-amine derivatives can inhibit PDE3. The analogues with the pyridone and pyrido[2,3-d]pyrimidin-4(3H)-one scaffolds inhibited both cAMP and cyclic guanosine monophosphate (cGMP) hydrolysis by PDE3, while the amine containing scaffolds were more selective for cGMP hydrolysis. This observation may set the base for substrate-selective pharmacological modulation of this important class of drug targets and with less side effects, particularly tachcardia. The dual inhibitors of PDE3 were more potent inhibitor towards the growth of HT-29 cancer cell lines. |
| تدمد: | 1347-5223 0009-2363 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d761a74f78bc8079ee427337d79614b8 https://doi.org/10.1248/cpb.c12-00993 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....d761a74f78bc8079ee427337d79614b8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13475223 00092363 |
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