Unconventional Knoevenagel-type indoles : Synthesis and cell-based studies for the identification of pro-apoptotic agents
Copyright © 2015 Elsevier Masson SAS. All rights reserved..
A new series of indole-based analogues were recently identified as potential anticancer agents. The Knoevenagel-type indoles herein presented were prepared via a one-pot condensation of iminium salts with active methylene reagents and were isolated as single geometric isomers. Biological evaluation in different cell-based assays revealed an antiproliferative activity for some analogues already in the nanomolar range against leukaemia, breast and renal cancer cell lines. To explain these effects, the most promising analogues of the series were engaged in further cell-based studies. Compounds 5e, l, p and 6a, b highlighted a pro-apoptotic potential being able to induce apoptosis in HL60, K562 and MCF-7 cell lines in a dose and time-dependent manner. The ability of these compounds to arrest cell cycle at the G2/M phase inspired the immunofluorescence studies which allowed us to identify tubulin as a potential target for compounds 5l and 6b.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2015 |
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| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:102 |
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| Enthalten in: |
European journal of medicinal chemistry - 102(2015) vom: 18. Sept., Seite 648-60 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Spallarossa, Andrea [VerfasserIn] |
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| Links: |
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| Themen: |
Antineoplastic Agents |
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| Anmerkungen: |
Date Completed 14.06.2016 Date Revised 12.09.2015 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ejmech.2015.08.009 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM252283961 |
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| 245 | 1 | 0 | |a Unconventional Knoevenagel-type indoles |b Synthesis and cell-based studies for the identification of pro-apoptotic agents |
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| 500 | |a Date Revised 12.09.2015 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2015 Elsevier Masson SAS. All rights reserved. | ||
| 520 | |a A new series of indole-based analogues were recently identified as potential anticancer agents. The Knoevenagel-type indoles herein presented were prepared via a one-pot condensation of iminium salts with active methylene reagents and were isolated as single geometric isomers. Biological evaluation in different cell-based assays revealed an antiproliferative activity for some analogues already in the nanomolar range against leukaemia, breast and renal cancer cell lines. To explain these effects, the most promising analogues of the series were engaged in further cell-based studies. Compounds 5e, l, p and 6a, b highlighted a pro-apoptotic potential being able to induce apoptosis in HL60, K562 and MCF-7 cell lines in a dose and time-dependent manner. The ability of these compounds to arrest cell cycle at the G2/M phase inspired the immunofluorescence studies which allowed us to identify tubulin as a potential target for compounds 5l and 6b | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Antiproliferative agents | |
| 650 | 4 | |a Indoles | |
| 650 | 4 | |a Pro-apoptotic agents | |
| 650 | 4 | |a Tubulin immunostaining | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a Indoles |2 NLM | |
| 700 | 1 | |a Caneva, Chiara |e verfasserin |4 aut | |
| 700 | 1 | |a Caviglia, Matteo |e verfasserin |4 aut | |
| 700 | 1 | |a Alfei, Silvana |e verfasserin |4 aut | |
| 700 | 1 | |a Butini, Stefania |e verfasserin |4 aut | |
| 700 | 1 | |a Campiani, Giuseppe |e verfasserin |4 aut | |
| 700 | 1 | |a Gemma, Sandra |e verfasserin |4 aut | |
| 700 | 1 | |a Brindisi, Margherita |e verfasserin |4 aut | |
| 700 | 1 | |a Zisterer, Daniela M |e verfasserin |4 aut | |
| 700 | 1 | |a Bright, Sandra A |e verfasserin |4 aut | |
| 700 | 1 | |a Williams, Clive D |e verfasserin |4 aut | |
| 700 | 1 | |a Crespan, Emmanuele |e verfasserin |4 aut | |
| 700 | 1 | |a Maga, Giovanni |e verfasserin |4 aut | |
| 700 | 1 | |a Sanna, Giuseppina |e verfasserin |4 aut | |
| 700 | 1 | |a Delogu, Ilenia |e verfasserin |4 aut | |
| 700 | 1 | |a Collu, Gabriella |e verfasserin |4 aut | |
| 700 | 1 | |a Loddo, Roberta |e verfasserin |4 aut | |
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