Gold(Ⅰ) organometallics with alkynyl and N-heterocyclic carbene ligands and their medicinal and computational chemistry evaluation as prospective anticancer drugs

Gold(Ⅰ) organometallics of the type alkynylgold(Ⅰ)(NHC) (where NHC = N-heterocyclic carbene) 5a – 5f and 6a/b were prepared and evaluated as prospective anticancer agents by computational and medicinal chemistry methods. DFT calculations showed similar stability for the series, with differing dipole moments, depending on the substituents on the alkynyl and the NHC ligands. Studies in cancer cell lines indicated in general that the complexes with the largest dipole moments exhibited the highest antiproliferative activity in comparison with structurally closely related complexes. Thus, complexes 5f, (with 4-fluoroethynylbenzene as alkynyl precursor), and 6b, (with mestranol as alkynyl precursor) containing the same methoxy‑substituted NHC ligand showed in general the strongest biological activity. Protein binding studies confirmed a high affinity to albumin (around 90 %) and cellular uptake studies indicated an increased uptake of the most active complex 5f.