Synthesis and characterization of novel naphthalene-derivatized tridentate ligands and their net neutral rhenium tricarbonyl complexes and cytotoxic effects on non-small cell lung cancer cells of interest

Abstract

Rhenium complexes have possible fluorescence imaging, radioimaging and therapeutic applications and can also serve as a model system for 99mTc. The quest for new pharmaceutical agents is thus an expanding area of research. In this study, we report two net neutral complexes, [Re(CO)3(N(SO2)(1-nap)dien)] and [Re(CO)3(N(SO2)(2-nap)dien)], synthesized by treating fac-[Re(CO)3(H2O)3]+ with two novel tridentate ligands, (N(SO2)(1-nap)dienH and N(SO2)(2-nap)dienH), derived from diethylenetriamine (dien) attached to a sulfonamide group. The compounds were characterized by UV–Visible, FTIR, 1H NMR and fluorescence spectroscopies, together with X-ray crystallography. It is evident from the 1H NMR spectroscopic data recorded in DMSO‑d6 as well as X-ray crystallography supported by FTIR data, that upon coordination to the metal centre, the sulfonamide nitrogen atom is deprotonated and the ligand binds with the metal in a tridentate fashion. Both the complexes have a distorted octahedral structure where the Re(I) metal is coordinated by three nitrogen atoms of the dien backbone and three CO ligands. Emission spectra were recorded in methanol and an enhanced fluorescence emission was observed in the 330–345 nm range for the ligands while the corresponding Re complexes showed no or quenched fluorescence intensities. The in vitro cytotoxic activity of the synthesized compounds was examined using NCI-H292 (non-small cell lung cancer cells) and MRC-5 (the human normal lung fibroblast cell line). The highest cytotoxic activity was observed for the [Re(CO)3(N(SO2)(1-nap)dien)] complex on NCI-H292 cells with an IC50 value of 9.91 μM at 48 h. However all four compounds show acute cytotoxicity for MRC-5 cells at 24 h. The promising cytotoxic activity of the novel ligands and metal complexes indicate that these compounds may be good candidates to be utilized as anticancer drug leads against lung cancer.