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Bispidine Analogues of Cisplatin, Carboplatin, and Oxaliplatin. Synthesis, Structures, and Cytotoxicity
journal contribution
posted on 2014-04-07, 00:00 authored by Huiling Cui, Richard Goddard, Klaus-Richard Pörschke, Alexandra Hamacher, Matthias
U. KassackBispidine (3,7-diazabicyclo[3.3.1]nonane,
C7H14N2) analogues of cisplatin,
carboplatin, and oxaliplatin
have been prepared. (C7H14N2)PtCl2·DMF (1b), obtained from (1,5-hexadiene)PtCl2 and bispidine in DMF, is dimeric in the solid state. Dissolving 1b in hot N-methylformamide allows crystallization
of the solvent-free polymeric (C7H14N2)PtCl2 (1a). Recrystallization of 1a,b from hot water yields the trihydrate (C7H14N2)PtCl2·3H2O
(1c). Reaction of 1 with Ag2(cbdca)
(cbdca = 1,1-cyclobutanedicarboxylate) in water affords the pentahydrate
(C7H14N2)Pt{C4H6(CO2)2}·5H2O (2b), which loses water in vacuo to give (C7H14N2)Pt{C4H6(CO2)2} (2a). Reaction of 1 with AgNO3 in water, followed by addition of Na2C2O4, affords the water-free polymeric (C7H14N2)Pt(C2O4) (3). All
complexes have been structurally characterized, revealing various
patterns of N–H···Cl and N–H···O
hydrogen bonds. In the hydrates 1c and 2b the complexes are embedded in intricate three-dimensional water
networks. Complexes 1a, 2a, and 3 have been tested for their cytotoxicity against human cancer cell
lines K562 (chronic myeloid leukemia), A2780 (ovarian cancer), and
its platinum-resistant subline A2780 CisR and are compared to their
parent analogues. The new complexes show significant cytotoxic activity
along with a low platinum resistance factor.