| Autor: |
Maciuca AM; Department of General and Inorganic Chemistry, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 6 Traian Vuia St, 020956 Bucharest, Romania., Munteanu AC; Department of General and Inorganic Chemistry, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 6 Traian Vuia St, 020956 Bucharest, Romania., Mihaila M; Center of Immunology, Stefan S. Nicolau Institute of Virology, 285 Mihai Bravu Ave, 030304 Bucharest, Romania., Badea M; Department of Inorganic Chemistry, Faculty of Chemistry, University of Bucharest, 90-92 Panduri Str, 050663 Bucharest, Romania., Olar R; Department of Inorganic Chemistry, Faculty of Chemistry, University of Bucharest, 90-92 Panduri Str, 050663 Bucharest, Romania., Nitulescu GM; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 6 Traian Vuia Str, 020956 Bucharest, Romania., Munteanu CVA; Department of Bioinformatics and Structural Biochemistry, Institute of Biochemistry of the Romanian Academy (IBRA), 296 Spl. Independenţei, 060031 Bucharest, Romania., Bostan M; Center of Immunology, Stefan S. Nicolau Institute of Virology, 285 Mihai Bravu Ave, 030304 Bucharest, Romania., Uivarosi V; Department of General and Inorganic Chemistry, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 6 Traian Vuia St, 020956 Bucharest, Romania. |
| Abstrakt: |
"Drug repositioning" is a current trend which proved useful in the search for new applications for existing, failed, no longer in use or abandoned drugs, particularly when addressing issues such as bacterial or cancer cells resistance to current therapeutic approaches. In this context, six new complexes of the first-generation quinolone oxolinic acid with rare-earth metal cations (Y 3+ , La 3+ , Sm 3+ , Eu 3+ , Gd 3+ , Tb 3+ ) have been synthesized and characterized. The experimental data suggest that the quinolone acts as a bidentate ligand, binding to the metal ion via the keto and carboxylate oxygen atoms; these findings are supported by DFT (density functional theory) calculations for the Sm 3+ complex. The cytotoxic activity of the complexes, as well as the ligand, has been studied on MDA-MB 231 (human breast adenocarcinoma), LoVo (human colon adenocarcinoma) and HUVEC (normal human umbilical vein endothelial cells) cell lines. UV-Vis spectroscopy and competitive binding studies show that the complexes display binding affinities (K b ) towards double stranded DNA in the range of 9.33 × 10 4 - 10.72 × 10 5 . Major and minor groove-binding most likely play a significant role in the interactions of the complexes with DNA. Moreover, the complexes bind human serum albumin more avidly than apo-transferrin. |
