Synthesis and antitumor effect in vitro and in vivo of substituted 1,3-dihydroindole-2-ones
Optimization of the anticancer activity for a class of compounds built on a 1,3-dihydroindole-2-one scaffold was performed. In comparison with recently published derivatives of oxyphenisatin the new analogues exhibited an equally potent antiproliferative activity in vitro and improved tolerability and activity in vivo. The best compounds from this series showed low nanomolar antiproliferative activity toward a series of cancer cell lines (compound (S)-38: IC(50) of 0.48 and 2 nM in MCF-7 (breast) and PC3 (prostate), respectively) and potent antitumor effects in well tolerated doses in xenograft models. The racemic compound (RS)-38 showed complete tumor regression at a dose of 20 mg/kg administered iv on days 1 and 7 in a PC3 rat xenograft.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2010 |
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| Erschienen: |
2010 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:53 |
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| Enthalten in: |
Journal of medicinal chemistry - 53(2010), 19 vom: 14. Okt., Seite 7140-5 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Christensen, Mette K [VerfasserIn] |
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| Links: |
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| Themen: |
3-cycloheptyl-3-(4-hydroxyphenyl)-6-methoxy-7-methylindolin-2-one |
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| Anmerkungen: |
Date Completed 09.11.2010 Date Revised 07.10.2010 published: Print Citation Status MEDLINE |
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| doi: |
10.1021/jm100763j |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM201611244 |
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| 500 | |a Date Revised 07.10.2010 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Optimization of the anticancer activity for a class of compounds built on a 1,3-dihydroindole-2-one scaffold was performed. In comparison with recently published derivatives of oxyphenisatin the new analogues exhibited an equally potent antiproliferative activity in vitro and improved tolerability and activity in vivo. The best compounds from this series showed low nanomolar antiproliferative activity toward a series of cancer cell lines (compound (S)-38: IC(50) of 0.48 and 2 nM in MCF-7 (breast) and PC3 (prostate), respectively) and potent antitumor effects in well tolerated doses in xenograft models. The racemic compound (RS)-38 showed complete tumor regression at a dose of 20 mg/kg administered iv on days 1 and 7 in a PC3 rat xenograft | ||
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| 700 | 1 | |a Erichsen, Kamille D |e verfasserin |4 aut | |
| 700 | 1 | |a Trojel-Hansen, Christina |e verfasserin |4 aut | |
| 700 | 1 | |a Tjørnelund, Jette |e verfasserin |4 aut | |
| 700 | 1 | |a Nielsen, Søren J |e verfasserin |4 aut | |
| 700 | 1 | |a Frydenvang, Karla |e verfasserin |4 aut | |
| 700 | 1 | |a Johansen, Tommy N |e verfasserin |4 aut | |
| 700 | 1 | |a Nielsen, Birgitte |e verfasserin |4 aut | |
| 700 | 1 | |a Sehested, Maxwell |e verfasserin |4 aut | |
| 700 | 1 | |a Jensen, Peter B |e verfasserin |4 aut | |
| 700 | 1 | |a Ikaunieks, Martins |e verfasserin |4 aut | |
| 700 | 1 | |a Zaichenko, Andrei |e verfasserin |4 aut | |
| 700 | 1 | |a Loza, Einars |e verfasserin |4 aut | |
| 700 | 1 | |a Kalvinsh, Ivars |e verfasserin |4 aut | |
| 700 | 1 | |a Björkling, Fredrik |e verfasserin |4 aut | |
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