Synthesis and biological studies of c(RGDyK) conjugates of cucurbitacins
Cucurbitacins (CUCUs) are triterpenoids known to display potent cytotoxic effects; however, their clinical application is limited due to poor pharmacokinetics and systemic toxicity. This work focuses on the development of c(RGDyK)-CUCU conjugates for the selective delivery of CUCUs to integrin-overexpressing cancer cells. The activity of the conjugates against various cancer cells was studied. They exhibited a mild cytostatic effect to six cancer cell lines and a cytotoxic effect against integrin-overexpressing MCF-7 and A549 cells. Their chemical and metabolic stability was extensively studied using LC-MS analysis. The conjugates maintained high affinity for αvβ3 integrin receptors. c(RGDyK) conjugation via a PEG linker was beneficial for CUCU-D and the resulting conjugate was approximately three-times more active than the free CUCU-D in MCF7 cells.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
Future medicinal chemistry - 13(2021), 10 vom: 15. Mai, Seite 877-895 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chatzisideri, Theodora [VerfasserIn] |
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| Links: |
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| Themen: |
60137-06-6 |
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| Anmerkungen: |
Date Completed 18.10.2021 Date Revised 18.10.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.4155/fmc-2020-0309 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM324129483 |
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| 520 | |a Cucurbitacins (CUCUs) are triterpenoids known to display potent cytotoxic effects; however, their clinical application is limited due to poor pharmacokinetics and systemic toxicity. This work focuses on the development of c(RGDyK)-CUCU conjugates for the selective delivery of CUCUs to integrin-overexpressing cancer cells. The activity of the conjugates against various cancer cells was studied. They exhibited a mild cytostatic effect to six cancer cell lines and a cytotoxic effect against integrin-overexpressing MCF-7 and A549 cells. Their chemical and metabolic stability was extensively studied using LC-MS analysis. The conjugates maintained high affinity for αvβ3 integrin receptors. c(RGDyK) conjugation via a PEG linker was beneficial for CUCU-D and the resulting conjugate was approximately three-times more active than the free CUCU-D in MCF7 cells | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a RGD peptide | |
| 650 | 4 | |a angiogenesis | |
| 650 | 4 | |a anticancer therapy | |
| 650 | 4 | |a cucurbitacins | |
| 650 | 4 | |a integrin avβ3 | |
| 650 | 4 | |a targeted drug delivery | |
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| 700 | 1 | |a Bousis, Spyridon |e verfasserin |4 aut | |
| 700 | 1 | |a Trafalis, Dimitrios |e verfasserin |4 aut | |
| 700 | 1 | |a Bianchini, Francesca |e verfasserin |4 aut | |
| 700 | 1 | |a Sarli, Vasiliki |e verfasserin |4 aut | |
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