Synthesis, characterization and antiproliferative studies of the enantiomers of cis-[(1,2-camphordiamine)dichloro]platinum(II) complexes.
The platinum(II) complex cis-[(1S,2R,3S)-1,7,7-trimethylbicyclo[2.2.1]heptane-2,3-diamine]dichloroplatinum(II) (1) and its enantiomer (2) have been synthesized and physically and spectroscopically characterized. To obtain the enantiopure complexes the chiral pool approach was applied. The synthetic pathway has four steps, starting from (+/-)-diphenylethylenediamine (DPEDA) (3) and the natural products (1S)-camphorquinone or (1R)-camphorquinone to obtain enantiomers 1 and 2, respectively. The interaction of the Pt(II) complexes with DNA was studied by several techniques: circular dichroism, electrophoresis on agarose gel and atomic force microscopy (AFM). These studies showed differences in the degree of interaction between both enantiomers and DNA (calf thymus DNA and plasmid pBR322 DNA). The cytotoxicity of enantiomers 1 and 2 against the HL-60 cell line was studied by in vitro tests of antiproliferative activity, incubating during both 24 h and 72 h. An important difference of activity was found between both enantiomers regarding the IC50 data at 24 h of incubation. Thus, complex 1 showed to be much more active than its enantiomer 2.
Montaña
Angel M
AM
Departamento de Química Orgánica, Universidad de Barcelona, Martí i Franquès 1-11, 08028 Barcelona, Spain. angel.montana@ub.edu
Bernal
Francisco J
FJ
Lorenzo
Julia
J
Farnós
Carlos
C
Batalla
Consuelo
C
Prieto
Maria J
MJ
Moreno
Virtudes
V
Avilés
Francesc X
FX
Mesas
Juan M
JM
Alegre
María-Teresa
MT
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002164:Camphor / Q000031:analogs & derivatives; D049109:Cell Proliferation / Q000187:drug effects*; D004247:DNA; D003959:Diamines; D005029:Ethylenediamines; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism
D000970:Antineoplastic Agents; D003959:Diamines; D005029:Ethylenediamines; D009944:Organoplatinum Compounds; C415332:camphordiamine; C518332:diphenylethylenediamine; D002164:Camphor; D004247:DNA