A new amido-phosphine of dichloroacetic acid as an active ligand for metals of pharmaceutical interest. Synthesis, characterization and tests of antiproliferative and pro-apoptotic activity.

We herein describe the synthesis and characterization of the new amido-phosphinic ligand 3,7‑bis(dichloroacetyl)‑1,3,7‑triaza‑5‑phosphabicyclo[3.3.1]nonane (DCP), a derivative of dichloroacetic acid (DCA), whose ability to reverse the suppressed mitochondrial apoptosis in cancer cells is known.

Solid lipid nanoparticles for the delivery of 1,3,5-triaza-7-phosphaadamantane (PTA) platinum (II) carboxylates.

The use of solid lipid nanoparticles (SLN) is a promising route for the delivery of platinum complexes aimed to anticancer activity. This paper describes the production and characterization of SLN suitable for the loading of Pt complexes containing the biocompatible phosphine 1,3,5-triaza-7-phosphaadamantane (PTA) as neutral ligand. After a screening of several lipidic phases, stearic acid-based SLN were identified as the most appropriate for the purpose.

Bis(dimethylsulfoxide)carbonateplatinum(ii), a new synthon for a low-impact, versatile synthetic route to anticancer Pt carboxylates.

The work describes a new low-impact synthetic route to Pt(ii)-carboxylate complexes, a class of compounds provided with established anticancer activity. The process is based on the ligand substitution on [PtCO3(Me2SO-S)2] (), a new synthon that can be easily prepared in water with high yield, is stable as a solid, and is reactive in solution where all its ligands can be easily replaced. It reacts with acidic O-donors releasing CO2 as the only side-product, whose development also supplies a driving force toward the products.

Lipid-based nanoparticles containing cationic derivatives of PTA (1,3,5-triaza-7-phosphaadamantane) as innovative vehicle for Pt complexes: Production, characterization and in vitro studies.

The aliphatic phosphine PTA (1,3,5-triaza-7-phosphaadamantane) is a promising ligand for metal complexes designed and developed as innovative inorganic drugs. In the present paper, an N-alkylated derivative of PTA, (PTAC16H33)X (X=I, C1, or X=PF6, C2) and its platinum coordination complex cis-[PtCl2(PTAC16H33)2](PF6)2, C3, were considered as components of cationic lipid nanoparticles (CLNs). Particularly, CLN1, CLN2 and CLN3 were obtained by adding derivatives C1, C2 or C3 during nanoparticles preparation, while CLN2-Pt were obtained by treating preformed CLN2 with Pt(II).

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.

Long-chain cationic derivatives of PTA (1,3,5-triaza-7-phosphaadamantane) as new components of potential non-viral vectors.

The purpose of this study was to investigate the potential of new positively charged solid lipid nanoparticles (SLN) to convey nucleic acids. The cationic character of SLN was obtained by adding as cationic molecules two different long-chain cationic phosphines (CP), namely hexadecyl-PTA iodide (CP16) and octadecyl-PTA iodide (CP18). The obtained CP-SLN are characterized by a positive charge on the surface and reproducible dimensions around 220 nm.

Water-soluble Cp ruthenium complex containing 1,3,5-triaza-7-phosphaadamantane and 8-thiotheophylline derivatives: synthesis, characterization, and antiproliferative activity.

The new water-soluble ruthenium(II) mononuclear complexes [RuCp(X)(PTA)(L)] (X = 8-thio-theophyllinate (TTH(-)), L = PTA (1), L = PPh(3) (7)); (X = 8-methylthio-theophyllinate (8-MTT(-)), L = PTA (2), L = PPh(3) (8)), (X = 8-benzylthio-theophyllinate (8-BzTT(-)), L = PTA (3), L = PPh(3) (9)) and binuclear complexes [{RuCp(PTA)(L)}(2)-μ-(Y-κN7,N'7)] (Y = bis(S-8-thiotheophyllinate)methane (MBTT(2-)), L = PTA (4), L = PPh(3) (10)), (Y = 1,2-bis(S-8-thiotheophyllinate)ethane (EBTT(2-)), L = PTA (5), L = PPh(3) (11)), (Y = 1,3-bis(S-8-thiotheophyllinate)propane (PBTT(2-)); L = PTA (6), L = PPh(3) (12)) have been synthesized and characterized by NMR, IR spectroscopy and elemental analysis. The single crystal X-ray structure of [RuCp(8-MTT-κS)(PTA)(2)] (2) was also obtained. The antiproliferative activity of the complexes on cisplatin-sensitive T2 and cisplatin-resistant SKOV3 cell lines has been evaluated.

Synthesis, characterization of strontium-bile acid salts and their bioactivity vs. the anti-osteoporosis drug strontium ranelate.

The strontium salts Sr(cholate)2, (Compound 1), Sr(dehydrocholate)2, (Compound 2) and Sr3(3-dehydrocholanoyliden-L-tartrate)2, (Compound 3) have been prepared and characterized. The potential anti-osteoporotic activity of these compounds was tested on human primary osteoblasts (hOBs) and human primary osteoclasts (hOCs) in comparison with the bioactivity of strontium ranelate, previously registered as drug in the treatment of post-menopausal osteoporosis. Our results led to the hypothesis that the tested compounds, particularly Compound 2, may have requirements for modulating skeletal tissue regeneration or at least down regulating the loss of bone mass.

Effects on erythroid differentiation of platinum(II) complexes of synthetic bile acid derivatives.

In this study, we compared some bile acid derivatives and their platinum(II) complexes with respect to their ability to induce erythroid differentiation of human leukemic K562 cells. The complexes analyzed were cis-[(3-dehydrocholanoyliden-L-tartrate)-diammineplatinum(II)] (compound 1) and cis-[di(dehydrocholanoate)-bis(triphenylphosphine)-platinum(II)] (compound 3), together with their free ligands, respectively, 3-dehydrocholanoyliden-L-tartaric acid (compound 2) and dehydrocholanoic acid (4), and their parent compounds, respectively, cisplatin and cis-[dichloride-bis(triphenylphosphine)-platinum(II)] (5). We found that compound 1 stimulates erythroid differentiation of K562 cells and an increase of fetal hemoglobin (HbF) production in erythroid precursor cells isolated from peripheral blood of human subjects.