Acetylcholine-like and Trimethylglycine-like PTA (1,3,5-Triaza-7-phosphaadamantane) Derivatives for the Development of Innovative Ru- and Pt-Based Therapeutic Agents

The PTA N-alkyl derivatives (PTAC2H4OCOMe)X (1X:1a, X = Br; 1b,X=I; 1c, X=PF6; 1d, X = BPh4), (PTACH2COOEt)X (2X: 2a, X = Br; 2b, X = Cl; 2c,X=PF6), and (PTACH2CH2COOEt)X (3X: 3a, X = Br; 3c, X=PF6), presenting all the functional groups of the natural cationic compounds acetylcholine or trimethylglycine combined with a P-donor site suitable for metal ion coordination, were prepared and characterized by NMR, ESI-MS, and elemental analysis. The X-ray crystal structures of 1d and 2c were determined. Ligands 1c, 2b, and 3c were coordinated to Pt(II) and Ru(II) to give the cationic complexes cis-[PtCl2(L)2]X2 and [RuCpCl(PPh3)(L)]X (L=1, 2, 3,X=Cl or PF6) designed with a structure targeted for anticancer activity. The X-ray crystal structure of [CpRu(PPh3)PTAC2H4OCOMe)Cl]PF6 (1c Ru) was deter-mined. The antiproliferative activity of the ligands and the complexes was evaluated on three human cancer cell lines.