Platinum-based antitumor drugs containing enantiomerically pure alpha-trifluoromethyl alanine as ligand.
Synthetic amino acids such as fluorinated alpha-amino acids are currently actively investigated for their biological activity. Herein, we report on the synthesis and characterization of platinum complexes containing an N,O-chelated pure enantiomer of alpha-trifluoromethylalanine (alpha-Tfm-Ala). The compounds are either anionic, K[PtCl2(alpha-Tfm-Ala)], or cationic, [PtAm2(alpha-Tfm-Ala)](NO3) (Am2= (NH3)2, ethylendiamine (en), 1,10-phenanthroline (phen), and 2,9-dimethyl-1,10-phenanthroline (Me2phen)). All complexes are highly soluble in water and have been fully characterized by NMR spectroscopy. In vitro cytotoxicity assays on different human tumor cell lines have been performed on some of the isolated compounds. [Pt(NH3)2(alpha-Tfm-Ala)] with R configuration of the amino acid proved to have an activity comparable to that of the reference compound cisplatin. Flow cytometric analysis on NCI-H460 tumor cells (absence of G2/M arrest, which instead is observed in the case of cisplatin) suggests a mechanism of action different from that of cisplatin.
Margiotta
Nicola
N
Dipartimento Farmaco-Chimico, Università di Bari, Via E. Orabona 4, I-70125 Bari, Italy.
Papadia
Paride
P
Lazzaro
Francesco
F
Crucianelli
Marcello
M
De Angelis
Francesco
F
Pisano
Claudio
C
Vesci
Loredana
L
Natile
Giovanni
G
D000409:Alanine / Q000031:analogs & derivatives* / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D008024:Ligands; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D008024:Ligands; D009944:Organoplatinum Compounds; C507723:alpha-trifluoromethylalanine; D000409:Alanine