Platinum N-Heterocyclic Carbene Complexes Based on Adenosine: Synthesis and Antiproliferative Studies.

Platinum(II) N-heterocyclic carbene complexes based on 2-chloroadenosine are synthesized. The reaction of 2-chloro-2',3',5'-tri-O-acetyladenosine 1 with Pt(PPh3)4 by C-Cl oxidative addition yields complex 2, with a PtII center bond to the C-2 of the purine ring. Complex 2 reacts with methyl iodide to yield N-heterocyclic carbene 3, which is subsequently deprotected under basic conditions to provide N-heterocyclic carbene 4, bearing a fully deprotected ribose. The compounds are tested for their cytotoxic activity in five different cell lines: L929, HEK293, A375, MDA-MB-231, and MCF-7. Among the platinum compounds, compound 2, the neutral compound bearing an anionic adenosyl ligand, provides the highest cytotoxic activity, particularly against the A375 and MDA-MB-231 cell lines. Encapsulation of compound 2 with nanostructured lipid carriers does not lead to an improvement in the cytotoxic activity.