Title:
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Lamellarin D bioconjugates I: synthesis and cellular internalization of PEG-derivatives
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Author:
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Pla Queral, Daniel; Francesch, Andrés; Calvo, Pilar; Cuevas, Carmen; Aligué i Alemany, Rosa Maria; Albericio Palomera, Fernando; Álvarez Domingo, Mercedes
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Other authors:
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Universitat de Barcelona |
Abstract:
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Herein is reported the design and synthesis of poly(ethylene glycol) derivatives of Lamellarin D with the aim of modulating their physicochemical properties, and improving the biological activity. Mono-, di- and tri-PEG conjugates with improved solubility were obtained in 18-57% overall yields from the corresponding partially protected phenolic derivatives of Lamellarin D. Conjugates 1-9 were tested in a panel of three human tumor cell lines (MDA-MB-231 breast, A-549 lung and HT-29 colon) to evaluate their cytotoxicity. Several compounds exhibited enhanced cellular internalization, and more than 85% of the derivatives showed a lower GI50 than Lam-D. Furthermore, cell cycle arrest at G2 phase, and apoptotic cell-death pathways were determined for Lamellarin D and these derivatives. |
Subject(s):
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-Compostos heterocíclics -Medicaments antineoplàstics -Transport biològic -Isoquinolina -Heterocyclic compounds -Antineoplastic agents -Biological transport -Isoquinoline |
Rights:
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(c) American Chemical Society , 2009
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Document type:
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Article Article - Accepted version |
Published by:
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American Chemical Society
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