Cargando…
Synthesis of spiro[isoindole-1,5’-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction
A series of spiro[isoindole-1,5-isoxazolidin]-3(2H)-ones has been synthesized by 1,3-dipolar cycloaddition of N-benzylnitrone with isoindolin-3-methylene-1-ones. The regio- and stereoselectivity of the process have been rationalized by computational methods. The obtained compounds show cytotoxic pro...
| Autores principales: | , , , , , , , , , , |
|---|---|
| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Beilstein-Institut
2016
|
| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5238597/ https://www.ncbi.nlm.nih.gov/pubmed/28144352 http://dx.doi.org/10.3762/bjoc.12.278 |
| _version_ | 1782495733845327872 |
|---|---|
| author | Giofrè, Salvatore V Cirmi, Santa Mancuso, Raffaella Nicolò, Francesco Lanza, Giuseppe Legnani, Laura Campisi, Agata Chiacchio, Maria A Navarra, Michele Gabriele, Bartolo Romeo, Roberto |
| author_facet | Giofrè, Salvatore V Cirmi, Santa Mancuso, Raffaella Nicolò, Francesco Lanza, Giuseppe Legnani, Laura Campisi, Agata Chiacchio, Maria A Navarra, Michele Gabriele, Bartolo Romeo, Roberto |
| author_sort | Giofrè, Salvatore V |
| collection | PubMed |
| description | A series of spiro[isoindole-1,5-isoxazolidin]-3(2H)-ones has been synthesized by 1,3-dipolar cycloaddition of N-benzylnitrone with isoindolin-3-methylene-1-ones. The regio- and stereoselectivity of the process have been rationalized by computational methods. The obtained compounds show cytotoxic properties and antiproliferative activity in the range of 9–22 μM. Biological tests suggest that the antitumor activity could be linked to the inhibition of the protein–protein p53-MDM2 interaction. Docking measurements support the biological data. |
| format | Online Article Text |
| id | pubmed-5238597 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2016 |
| publisher | Beilstein-Institut |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-52385972017-01-31 Synthesis of spiro[isoindole-1,5’-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction Giofrè, Salvatore V Cirmi, Santa Mancuso, Raffaella Nicolò, Francesco Lanza, Giuseppe Legnani, Laura Campisi, Agata Chiacchio, Maria A Navarra, Michele Gabriele, Bartolo Romeo, Roberto Beilstein J Org Chem Full Research Paper A series of spiro[isoindole-1,5-isoxazolidin]-3(2H)-ones has been synthesized by 1,3-dipolar cycloaddition of N-benzylnitrone with isoindolin-3-methylene-1-ones. The regio- and stereoselectivity of the process have been rationalized by computational methods. The obtained compounds show cytotoxic properties and antiproliferative activity in the range of 9–22 μM. Biological tests suggest that the antitumor activity could be linked to the inhibition of the protein–protein p53-MDM2 interaction. Docking measurements support the biological data. Beilstein-Institut 2016-12-20 /pmc/articles/PMC5238597/ /pubmed/28144352 http://dx.doi.org/10.3762/bjoc.12.278 Text en Copyright © 2016, Giofrè et al. https://creativecommons.org/licenses/by/4.0https://www.beilstein-journals.org/bjoc/termsThis is an Open Access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The license is subject to the Beilstein Journal of Organic Chemistry terms and conditions: (https://www.beilstein-journals.org/bjoc/terms) |
| spellingShingle | Full Research Paper Giofrè, Salvatore V Cirmi, Santa Mancuso, Raffaella Nicolò, Francesco Lanza, Giuseppe Legnani, Laura Campisi, Agata Chiacchio, Maria A Navarra, Michele Gabriele, Bartolo Romeo, Roberto Synthesis of spiro[isoindole-1,5’-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction |
| title | Synthesis of spiro[isoindole-1,5’-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction |
| title_full | Synthesis of spiro[isoindole-1,5’-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction |
| title_fullStr | Synthesis of spiro[isoindole-1,5’-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction |
| title_full_unstemmed | Synthesis of spiro[isoindole-1,5’-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction |
| title_short | Synthesis of spiro[isoindole-1,5’-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction |
| title_sort | synthesis of spiro[isoindole-1,5’-isoxazolidin]-3(2h)-ones as potential inhibitors of the mdm2-p53 interaction |
| topic | Full Research Paper |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5238597/ https://www.ncbi.nlm.nih.gov/pubmed/28144352 http://dx.doi.org/10.3762/bjoc.12.278 |
| work_keys_str_mv | AT giofresalvatorev synthesisofspiroisoindole15isoxazolidin32honesaspotentialinhibitorsofthemdm2p53interaction AT cirmisanta synthesisofspiroisoindole15isoxazolidin32honesaspotentialinhibitorsofthemdm2p53interaction AT mancusoraffaella synthesisofspiroisoindole15isoxazolidin32honesaspotentialinhibitorsofthemdm2p53interaction AT nicolofrancesco synthesisofspiroisoindole15isoxazolidin32honesaspotentialinhibitorsofthemdm2p53interaction AT lanzagiuseppe synthesisofspiroisoindole15isoxazolidin32honesaspotentialinhibitorsofthemdm2p53interaction AT legnanilaura synthesisofspiroisoindole15isoxazolidin32honesaspotentialinhibitorsofthemdm2p53interaction AT campisiagata synthesisofspiroisoindole15isoxazolidin32honesaspotentialinhibitorsofthemdm2p53interaction AT chiacchiomariaa synthesisofspiroisoindole15isoxazolidin32honesaspotentialinhibitorsofthemdm2p53interaction AT navarramichele synthesisofspiroisoindole15isoxazolidin32honesaspotentialinhibitorsofthemdm2p53interaction AT gabrielebartolo synthesisofspiroisoindole15isoxazolidin32honesaspotentialinhibitorsofthemdm2p53interaction AT romeoroberto synthesisofspiroisoindole15isoxazolidin32honesaspotentialinhibitorsofthemdm2p53interaction |