Synthesis, characterisation and in vitro cytotoxicity studies of a series of chiral platinum(II) complexes based on the 2-aminomethylpyrrolidine ligand: X-ray crystal structure of [PtCl2(R-dimepyrr)] (R-dimepyrr=N-dimethyl-2(R)-aminomethylpyrrolidine).
A series of platinum(II) complexes were synthesised based on the enantiomerically pure amino acid proline. Novel synthetic pathways were developed, adapted from standard peptide chemistry, to produce the 2-aminomethylpyrrolidine (pyrr) ligand and its derivatives with differing arrangements of methyl substituents at the exocyclic amine sites. The crystal structure of [PtCl(2)(R-dimepyrr)] (R-dimepyrr=N,N-dimethyl-2(R)-aminomethylpyrrolidine) is reported and the five-membered ligand ring has been shown to be in an envelope conformation. Cytotoxicity studies were carried out on the ovarian cancer A2780 tumour cell line and its cisplatin-resistant variant, A2780cisR. Remarkably good activity was seen for several of the drugs when compared to cisplatin despite the addition of substantial steric bulk to the amine groups, and there was a lack of cross-resistance with cisplatin seen for some compounds.
Diakos
Connie I
CI
School of Chemistry, The University of Sydney, Sydney, NSW, Australia.
Zhang
Mei
M
Beale
Philip J
PJ
Fenton
Ronald R
RR
Hambley
Trevor W
TW
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010984:Platinum / Q000737:chemistry*; D011392:Proline / Q000737:chemistry; D011759:Pyrrolidines / Q000737:chemistry*; D013237:Stereoisomerism
D000970:Antineoplastic Agents; D008024:Ligands; D009942:Organometallic Compounds; D011759:Pyrrolidines; D010984:Platinum; D011392:Proline; C032519:pyrrolidine