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 (PTAC(2)H(4)OCOMe)X (1X: 1a, X = Br; 1b, X = 1; 1c, X = PF6; 1d, X = BPh4), (PTACH(2)COOEt)X (2X: 2a, X = Br; 2b, X = Cl; 2c, X = PF6), and (PTACH(2)CH(2)COOEt)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)]X-2 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)(PTAC(2)H(4)OCOMe)Cl]PF6 (1cRu) was determined. The antiproliferative activity of the ligands and the complexes was evaluated on three human cancer cell lines.