title: Bispidine analogues of cisplatin, carboplatin, and oxaliplatin. synthesis, structures, and cytotoxicity.
abstract: Bispidine (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.
authors.affiliation: Max-Planck-Institut für Kohlenforschung , Kaiser-Wilhelm-Platz 1, D-45470 Mülheim an der Ruhr, Germany.
authors.forename: Huiling
authors.initials: H
authors.lastname: Cui
authors.forename: Richard
authors.initials: R
authors.lastname: Goddard
authors.forename: Klaus-Richard
authors.initials: KR
authors.lastname: Pörschke
authors.forename: Alexandra
authors.initials: A
authors.lastname: Hamacher
authors.forename: Matthias U
authors.initials: MU
authors.lastname: Kassack
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000633:toxicity*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry*; D016190:Carboplatin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000633:toxicity*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000633:toxicity*; D004396:Coloring Agents; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000633:toxicity*; D000077150:Oxaliplatin; D013329:Structure-Activity Relationship; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004396:Coloring Agents; D009944:Organoplatinum Compounds; D013778:Tetrazolium Salts; D013844:Thiazoles; C495809:bispidine; D000077150:Oxaliplatin; D016190:Carboplatin; C022616:thiazolyl blue; D002945:Cisplatin