title: Lamellarin D bioconjugates I: Synthesis and cellular internalization of PEG-derivatives.
abstract: 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 GI(50) than Lam-D. Furthermore, cell cycle arrest at G2 phase and apoptotic cell-death pathways were determined for Lamellarin D and these derivatives.
authors.affiliation: Institute for Research in Biomedicine, Barcelona Science Park-University of Barcelona, and CIBER-BBN Networking Centre on Bioengineering, Biomaterials, and Nanomedicine, Baldiri Reixac 10, E-08028 Barcelona, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Pla
authors.forename: Andrés
authors.initials: A
authors.lastname: Francesch
authors.forename: Pilar
authors.initials: P
authors.lastname: Calvo
authors.forename: Carmen
authors.initials: C
authors.lastname: Cuevas
authors.forename: Rosa
authors.initials: R
authors.lastname: Aligué
authors.forename: Fernando
authors.initials: F
authors.lastname: Albericio
authors.forename: Mercedes
authors.initials: M
authors.lastname: Alvarez
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D001692:Biological Transport; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D003374:Coumarins; D006576:Heterocyclic Compounds, 4 or More Rings; D007546:Isoquinolines; C455554:lamellarin D; D011092:Polyethylene Glycols