Publication
(Pentamethylcyclopentadienato)rhodium Complexes for Delivery of the Curcumin Anticancer Drug
Publisher:
Wiley
Date:
16-02-2017
DOI:
10.1002/EJIC.201601331
Abstract: [Rh III (*Cp)Cl(X,Y)] n + complexes {X, Y = Cl, PTA, n = 0 ( 2 ) X, Y = en, n = 1 ( 3 , Cl – salt 4 , PF 6 – salt) X, Y = acac, n = 0 ( 5 ) X, Y = cur, n = 0 ( 6 ), where *Cp = pentamethylcyclopentadienato, curH = curcumin PTA = 1,3,5‐triaza‐7‐phosphatricyclo[3.3.1.1]decane en = 1,2‐ethanediamine acac = acetylacetonato = 2,4‐pentanedionato(1–)} were synthesized from [Rh(*Cp)(µ‐Cl)Cl] 2 ( 1 ). While 2 – 5 were inactive against human epithelial A549 lung‐cancer cells in assays of cytotoxicity, and antimetastatic and proapoptotic behaviors, 6 had a cytotoxic activity similar to that of curH over 72 h, but at 24 h in real‐time cell migration assays, it was less active, showing slow release of curH. All complexes underwent ligand‐exchange reactions with biomolecules and cells within the timeframes of the assays (X‐ray absorption spectroscopy). Intracellular elemental distributions (X‐ray fluorescence microscopy) showed that 6 effectively delivered curH to cells, where it was released. Other elemental distributions and caspase activities were consistent with preapoptotic activities. As such, 6 is a promising delivery agent for bioactive ligands, such as curH. However, pure curcumin itself showed a previously unrecognized ability to promote migration of A549 cells at subtoxic concentrations in the presence of endothelial growth factor, which may be a concern for its widespread use as a nutritional supplement and as a potential drug. This aspect warrants further research.