İçsel, CeydaYılmaz, Veysel TAygün, MuhittinErkısa, MerveUlukaya, Engin2022-04-062022-04-062022Icsel, C., Yilmaz, V. T., Aygün, M., & Ulukaya, E. (2022). Novel 5-fluorouracil complexes of Zn (II) with pyridine-based ligands as potential anticancer agents. Dalton Transactions.https://doi.org/10.1039/d1dt04070ghttps://hdl.handle.net/20.500.12713/2618A series of novel Zn(II) complexes of 5-fluorouracilate (5-FU), namely [Zn(5-FU)2(bpy)] (1), [Zn(5-FU)2(phen)] (2), [Zn(5-FU)2(dpya)]·H2O (3), [Zn(5-FU)2(bpyma)]·2H2O (4) and [Zn(5-FU)2(terpy)]·H2O (5), were synthesized and structurally characterized by spectroscopic methods and X-ray crystallography. 5-FU was coordinated to Zn(II) via the deprotonated N3 site and also presented the N1 and N3 linkage isomerism in 4 and 5 due to its tautomerism. The antiproliferative activity of the complexes was studied against lung (A549), breast (MDA-MB-231), colon (HCT116) and prostate (DU145) cancer cell lines. Complexes 1, 4 and 5 except 2 and 3 showed potent growth inhibitory activity towards selected cancer cells. Remarkably, 4 was highly cytotoxic towards A549 and MDA-MB-231 cell lines, being more active than the clinical drugs cisplatin and 5-FU. In addition, 4 was not toxic to normal lung cells (BEAS-2B). The complex exhibited a significantly high affinity towards DNA as assessed by gel electrophoresis and DNA docking. The mechanistic studies of 4 in A549 cells indicated that the complex induced apoptotic cell death as evidenced via caspase 3/7 activity, Bcl2 inactivation, annexin V and DAPI/PI staining. 4 further elevated the levels of reactive oxygen species (ROS), depolarized mitochondria and enhanced the expression of ?-H2AX, thus contributing to its remarkable anticancer activity.eninfo:eu-repo/semantics/closedAccessArticle1335275157WOS:0007674811000012-s2.0-85127028175Q110.1039/d1dt04070gN/A