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)](2)Br-2 1 and a bimetallic bridged gold complex [Au-2(C13H13N5)Cl-2](2) derived from 2,6-bis(3-methylimidazolin-2-yliden-1-yl)pyridine dibromide L1 have been synthesized and fully characterized by IJV-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. (C) 2016 Elsevier Ltd. All rights reserved.