Quinoline- and coumarin-based ligands and their rhenium(I) tricarbonyl complexes: synthesis, spectral characterization and antiproliferative activity on T-cell lymphoma

Abstract

Novel 6-substituted 2-(trifluoromethyl)quinoline 5a–5e and coumarin 6a–6d ligands with aldoxime ether linked pyridine moiety were synthesized by O-alkylation of quinoline and coumarin with (E)-picolinaldehyde oxime and subsequently with [Re(CO)₅Cl] gave rhenium(I) tricarbonyl complexes 5a_Re–5e_Re and 6a_Re–6d_Re that were fully characterized by NMR, single-crystal X-ray diffraction, IR and UV–Vis spectroscopy. The results of antiproliferative evaluation of quinoline and coumarin ligands and their rhenium(I) tricarbonyl complexes on various human tumor cell lines, including acute lymphoblastic leukemia (CCRF-CEM), acute monocytic leukemia (THP1), cervical adenocarcinoma (HeLa), colon adenocarcinoma (CaCo-2), T-cell lymphoma (HuT78), and non-tumor human fibroblasts (BJ) showed that the quinoline complexes 5a_Re–5e_Re had higher inhibitory activity than coumarin complexes 6a_Re–6d_Re, particularly against T-cell lymphoma (HuT78) cells. 6-Methoxy-2-(trifluoromethyl)quinoline 5e and 6-methylcoumarin 6d, and their rhenium(I) tricarbonyl complexes 5e_Re and 6d_Re were found to arrest the cell cycle of HuT78 cells by causing a significant accumulation of cells in the G0/G1 phase and a marked decrease in the number of cells in the G2/M phase. These rhenium(I) tricarbonyl complexes also slightly increased ROS production and significantly decreased the mitochondrial membrane potential by 50 % (5e_Re) and 45 % (6d_Re) compared to untreated cells and cells treated with 5e and 6d. These results suggest that the cytotoxic effects of these compounds are mediated by their effects on mitochondrial membrane potential and the subsequent increase in ROS production.