دورية أكاديمية
Design of new quinolin-2-one-pyrimidine hybrids as sphingosine kinases inhibitors
| العنوان: | Design of new quinolin-2-one-pyrimidine hybrids as sphingosine kinases inhibitors |
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| المؤلفون: | Vettorazzi, Marcela Cristina, Insuasty, Daniel, Lima, Santiago, Gutierrez, Lucas Joel, Nogueras, Manuel, Marchal, Antonio, Abonia, Rodrigo, Andujar, Sebastian Antonio, Spiegel, Sarah, Cobo, Justo, Enriz, Ricardo Daniel |
| بيانات النشر: | Academic Press Inc Elsevier Science |
| المجموعة: | CONICET Digital (Consejo Nacional de Investigaciones Científicas y Técnicas) |
| مصطلحات موضوعية: | Sphingosine kinase 1 inhibitors, Quinolin-2-one-pyrimidine hybrids, Synthesis, Bioassays, Molecular modelling, https://purl.org/becyt/ford/1.4Test, https://purl.org/becyt/ford/1Test |
| الوصف: | Sphingosine-1-phosphate is now emerging as an important player in cancer, inflammation, autoimmune, neurological and cardiovascular disorders. Abundance evidence in animal and humans cancer models has shown that SphK1 is linked to cancer. Thus, there is a great interest in the development new SphK1 inhibitors as a potential new treatment for cancer. In a search for new SphK1 inhibitors we selected the well-known SKI-II inhibitor as the starting structure and we synthesized a new inhibitor structurally related to SKI-II with a significant but moderate inhibitory effect. In a second approach, based on our molecular modeling results, we designed new structures based on the structure of PF-543, the most potent known SphK1 inhibitor. Using this approach, we report the design, synthesis and biological evaluation of a new series of compounds with inhibitory activity against both SphK1 and SphK2. These new inhibitors were obtained incorporating new connecting chains between their polar heads and hydrophobic tails. On the other hand, the combined techniques of molecular dynamics simulations and QTAIM calculations provided complete and detailed information about the molecular interactions that stabilize the different complexes of these new inhibitors with the active sites of the SphK1. This information will be useful in the design of new SphK inhibitors. ; Fil: Vettorazzi, Marcela Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina ; Fil: Insuasty, Daniel. Universidad de Jaén; España ; Fil: Lima, Santiago. Virginia Commonwealth University School of Medicine; Estados Unidos ; Fil: Gutierrez, Lucas Joel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0045-2068 |
| العلاقة: | info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0045206819312362Test; http://hdl.handle.net/11336/118780Test; Vettorazzi, Marcela Cristina; Insuasty, Daniel; Lima, Santiago; Gutierrez, Lucas Joel; Nogueras, Manuel; et al.; Design of new quinolin-2-one-pyrimidine hybrids as sphingosine kinases inhibitors; Academic Press Inc Elsevier Science; Bioorganic Chemistry; 94; 103414; 1-2020; 1-20; CONICET Digital; CONICET |
| الإتاحة: | https://doi.org/10.1016/j.bioorg.2019.103414Test http://hdl.handle.net/11336/118780Test |
| حقوق: | info:eu-repo/semantics/restrictedAccess ; https://creativecommons.org/licenses/by-nc-sa/2.5/arTest/ |
| رقم الانضمام: | edsbas.38D61147 |
| قاعدة البيانات: | BASE |
| تدمد: | 00452068 |
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