Novel structures of platinum complexes bearing N‑bisphosphonates and study of their biological properties

• Published in: Journal of inorganic biochemistry Vol. 191; pp. 112 - 118
• Main Authors: Alvarez-Valdes, Amparo, Matesanz, Ana I., Perles, Josefina, Fernandes, Célia, Correia, João D.G., Mendes, Filipa, Quiroga, Adoracion G.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-02-2019
• Subjects: Animals; Bisphosphonates; Cattle; Cell Line, Tumor; Crystallography, X-Ray; Diphosphonates - chemistry; Diphosphonates - pharmacology; DNA; DNA - drug effects; Humans; Hydroxyapatite; Platinum complexes; Platinum Compounds - chemistry; Platinum Compounds - pharmacology; Hydroxyapatite; Bisphosphonates; DNA; Platinum complexes
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2018.11.010

Novel bisphosphonate platinum complexes: [Pt(isopropylamine)2(BP)]NO3 (BP = pamidronate and alendronate) have been synthesized and characterized. Their monomeric structure contains a bisphosphonate acting as chelate ligand through its oxygen atom donors, conferring the compound's cationic structure with a good solubility in water. The study of the compounds in solution showed high stability up to 24 h. The cytotoxicity in cancer cell lines has been assessed. We also present preliminary studies on the evaluation of the affinity towards biological targets such as DNA (both calf thymus DNA and supercoiled plasmid DNA) and hydroxyapatite where the complexes showed a low DNA interaction, but a clear affinity for hydroxyapatite comparing to their precursors.
The monomeric bisphosphonate platinum complexes structures possess water solubility and high stability. Preliminary studies on the evaluation of the complexes' affinity towards DNA (Calf Thymus and plasmid DNA) and hydroxyapatite showed low DNA interaction, but clear affinity for hydroxyapatite compared with the free biphosphonate. [Display omitted]
•Two monomeric and cationic Pt complexes show water solubility and high stability.•Characterization data indicate that bisphosphonate acts as chelate ligand.•The crystallographic data corroborate the structure.•Cytotoxic activity has been assessed in several tumor cell lines.•Preliminary studies demonstrate the affinity towards DNA and hydroxyapatite.