title: Double targeting of tumours with pyrenyl-modified dendrimers encapsulated in an arene-ruthenium metallaprism.
abstract: The self-assembly of 2,4,6-tris(pyridin-4-yl)-1,3,5-triazine (tpt) triangular panels with p-cymene-ruthenium building blocks and 5,8-dioxido-1,4-naphthoquinonato (donq) bridges, in the presence of pyrenyl-containing dendrimers of different generations (P(0), P(1) and P(2)), affords the triangular prismatic host-guest compounds [P(n)⊂Ru(6)(p-cymene)(6)(tpt)(2)(donq)(3)](6+) ([P(n)⊂1](6+)). The host-guest nature of these systems, with the pyrenyl moiety being encapsulated in the hydrophobic cavity of the cage and the dendritic functional group pointing outwards, was confirmed by NMR spectroscopy ((1)H, 2D and DOSY). The host-guest properties of these systems were studied in solution by NMR and UV/Vis spectroscopic methods, allowing the determination of their affinity constants (K(a)). Moreover, the ability of these water-soluble host-guest systems to carry the pyrenyl-containing dendrimers into cancer cells was evaluated on human ovarian cancer cells. The host-guest systems are all more cytotoxic than the empty cage [1][CF(3)SO(3)](6) (IC(50)≈4 μM), with the most active compound, [P(0)⊂1][CF(3)SO(3)](6), being an order of magnitude more cytotoxic.
authors.affiliation: Institut de Chimie, Université de Neuchâtel, Avenue de Bellevaux 51, 2000 Neuchâtel, Switzerland.
authors.forename: Anaïs
authors.initials: A
authors.lastname: Pitto-Barry
authors.forename: Nicolas P E
authors.initials: NP
authors.lastname: Barry
authors.forename: Olivier
authors.initials: O
authors.lastname: Zava
authors.forename: Robert
authors.initials: R
authors.lastname: Deschenaux
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Dyson
authors.forename: Bruno
authors.initials: B
authors.lastname: Therrien
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology; D050091:Dendrimers / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011721:Pyrenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012428:Ruthenium / Q000737:chemistry*; D014227:Triazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D050091:Dendrimers; D009942:Organometallic Compounds; D011721:Pyrenes; D014227:Triazines; D012428:Ruthenium; D002945:Cisplatin