Remarkable in vitro anti-HIV activity of new silver(I)– and gold(I)–N-heterocyclic carbene complexes. Synthesis, DNA binding and biological evaluation

A novel metallomacrocyclic silver complex [Ag(C13H13N5)]2Br21 and a bimetallic bridged gold complex [Au2(C13H13N5)Cl2] 2 derived from 2,6-bis(3-methylimidazolin-2-yliden-1-yl)pyridine dibromide L1 have been synthesized and fully characterized by UV–Vis, elemental analysis, FT-IR, NMR techniques and DFT calculations. The DNA interactions with the compounds were investigated by UV-spectrophotometric studies, viscosity measurements and DNA electrophoresis. Additionally, the lipophilicity values were determined from the water/n-octanol partition coefficient. Experimental data indicated that all the compounds interacted with DNA, through a non-covalent binding mode. L1 and 2 were found to be hydrophilic character while 1 was somewhat lipophilic. The biological activities of L1, 1 and 2 were tested against a panel of cancer cell lines (MCF-7, PC-3, A459, HeLa, HT-29 and the 4T1 murine tumor cell line). In vitro antiviral studies against HIV-1 were performed in infected MT4 leukemia cells. All the compounds exhibited a low activity against the cell lines, associated possibly with low lipophilicity values. However, complexes 1 and 2 showed remarkable viral inhibition at low concentrations. The complexes may inhibit virus infectivity through interaction with the HIV-1 envelope proteins.

Two novel complexes of silver and gold with 2,6-bis(3-methylimidazolin-2-yliden-1-yl)pyridine dibromide were synthesized and characterized. Their biological activities were evaluated through of the binding to CT DNA and inhibition in tumor cell lines and MT4 cells infected with HIV-1. Inhibition of the viral activity was over 55% at low concentrations.Figure optionsDownload as PowerPoint slide