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Modified cap group suberoylanilide hydroxamic acid histone deacetylase inhibitor derivatives reveal improved selective antileukemic activity.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Salmi-Smail, Chanaz Fabre, Aurélie C. Dequiedt, Franck Restouin, Audrey Castellano, Renata Garbit, Slaveia Roche, Philippe Morelli, Xavier Brunel, Jean Michel Collette, Yves |
| Copyright Year | 2010 |
| Abstract | A series of SAHA cap derivatives was designed and prepared in good-to-excellent yields that varied from 49% to 95%. These derivatives were evaluated for their antiproliferative activity in several human cancer cell lines. Antiproliferative activity was observed for concentrations varying from 0.12 to >100 microM, and a molecular modeling approach of selected SAHA derivatives, based on available structural information of human HDAC8 in complex with SAHA, was performed. Strikingly, two compounds displayed up to 10-fold improved antileukemic activity with respect to SAHA; however, these compounds displayed antiproliferative activity similar to SAHA when assayed against solid tumor-derived cell lines. A 10-fold improvement in the leukemic vs peripheral blood mononuclear cell therapeutic ratio, with no evident in vivo toxicity toward blood cells, was also observed. The herein-described compounds and method of synthesis will provide invaluable tools to investigate the molecular mechanism responsible for the reported selectively improved antileukemic activity. |
| Starting Page | 233 |
| Ending Page | 244 |
| Page Count | 12 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://core.ac.uk/download/pdf/13470428.pdf |
| PubMed reference number | 20218673v1 |
| Alternate Webpage(s) | https://doi.org/10.1021/jm901358y |
| DOI | 10.1021/jm901358y |
| Journal | Journal of medicinal chemistry |
| Volume Number | 53 |
| Issue Number | 8 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Adverse reaction to drug Cultured Cell Line Forty Nine Histone Deacetylase 8 Histones Hydroxamic Acids Neoplasms Peripheral blood mononuclear cell (cell) Vorinostat cancer cell molecular modeling solid tumor therapeutic index |
| Content Type | Text |
| Resource Type | Article |
