Delivery of Floxuridine derivatives to cancer cells by water-soluble organometallic cages
Author(s)
Yi, Jeong Wu
Barry, Nicolas P. E.
Furrer, Mona A.
Zava, Olivier
Dyson, Paul J.
Kim, Byeang Hyean
Date issued
2012
In
Bioconjugate Chem.
Vol
3
No
23
From page
461
To page
471
Subjects
ruthenium arene water soluble cage compd prepn self assembly tripyridyl triazine dioxybenzoquinone dioxynaphthoquinone bridged ruthenium cymene complex prepn inclusion antitumor nucleoside conjugate ruthenium organometallic hydrophilic cage drug delivery antitumor nucleoside inclusion ruthenium organometallic hydrophilic cage
Abstract
Ruthenium water-sol. organometallic cage compds., assembled by 1,2,4,5-benzenetetrolato (dobq), 1,4,5,8-naphthalenetetrolato (donq) and 2,4,6-tri-4-pyridyl-1,3,5-triazine (tpt) ligands gave carceplex inclusion compds. I and II (L = ?6-cymene), resp., with amino acids and nucleoside antitumor agent, Floxuridine (2'-deoxy-5-fluorouridine) pyrene conjugates [R = (CH2)3CONHCHYCO2-5'-O-Floxuridine; Y = H, CH2Ph; R = (CH2)3CO2-5'-O-Floxuridine]. The self-assembly of tpt triangular panels with areneruthenium building blocks [(?6-p-cymene)RuCl]2Q (Q = dobq, donq) in the presence of a pyrenyl-nucleoside derivs. (1-R-pyrene), affords the triangular prismatic host-guest compds. I and II [(pyrene-R)?1]6+ and [(pyrene-R)?2]6+, resp. The inclusion of six monosubstituted pyrenyl-nucleosides [1-R-pyrene; R = R1-R6, where R1 = (CH2)3CO2-5'-O-2'-deoxyuridine, R2 = (CH2)3CO2-5-fluoro-5'-O-2'-deoxyuridine, R3 = (CH2)3CONHCH2CO2-5'-O-2'-deoxyuridine, R4 = (CH2)3CONHCH2CO2-5-fluoro-5'-O-2'-deoxyuridine, R5 = (CH2)3CONHCH(CH2Ph)2CO2-5'-O-2'-deoxyuridine, R6 = (CH2)3CONHCH(CH2Ph)CO2-5-fluoro-5'-O-2'-deoxyuridine] has been accomplished. The carceplex nature of [(pyrene-R)?1]6+ with the pyrenyl moiety firmly encapsulated in the hydrophobic cavity of the cage with the nucleoside groups pointing outward was confirmed by NMR spectroscopy and electrospray ionization mass spectrometry (ESI-MS), while the host-guest nature of [(pyrene-R)?2]6+ was studied in soln. by NMR techniques. In contrast to the floxuridine compds. used in the clinic, the host-guest complexes are highly water-sol. Consequently, the cytotoxicities of these water-sol. compds. have been established using human ovarian A2780 and A2780cisR cancer cells. All the host-guest systems are more cytotoxic than the empty cages alone ([1][CF3SO3]6, IC50 = 23 ?M; [2][CF3SO3]6, IC50 = 10 ?M), the most active compd. [1-R4-pyrene?1][CF3SO3]6 being 2 orders of magnitude more cytotoxic (IC50 = 0.3 ?M) on these human ovarian cancer cell lines (A2780 and A2780cisR). [on SciFinder(R)]
Publication type
journal article