Ni(ii)/Cu(ii)/Zn(ii) 5,5-diethylbarbiturate complexes with 1,10-phenanthroline and 2,2'-dipyridylamine: synthesis, structures, DNA/BSA binding, nuclease activity, molecular docking, cellular uptake, cytotoxicity and the mode of cell death.
New 5,5-diethylbarbiturate (barb) complexes of Ni(ii), Cu(ii) and Zn(ii) with 1,10-phenanthroline (phen) and 2,2'-dipyridylamine (dpya), namely [Ni(phen-κN,N')3]Cl(barb)·7H2O (), [Cu(barb-κN)(barb-κ(2)N,O)(phen-κN,N')]·H2O (), [Cu(barb-κN)2(phen-κN,N')] (), [Zn(barb-κN)2(phen-κN,N')]·H2O (), [Ni(barb-κ(2)N,O)(dpya-κN,N')2]Cl·2H2O (), [Cu(barb-κ(2)N,O)2(dpya-κN,N')]·2H2O () and [Zn(barb-κN)2(dpya-κN,N')] (), were synthesized and characterized by elemental analysis, UV-vis, FT-IR and ESI-MS. The structures of the complexes were determined by X-ray crystallography. Notably, and were fluorescent in MeOH : H2O at rt. The interaction of the complexes with fish sperm (FS) DNA and bovine serum albumin (BSA) was investigated in detail by various techniques. The complexes exhibited groove binding along with a partial intercalative interaction with DNA, while the hydrogen bonding and hydrophobic interactions played a major role in binding to BSA. It is noteworthy that exhibited the highest affinity towards DNA and BSA. Enzyme inhibition assay showed that show a preference for both A/T and G/C rich sequences in pUC19 DNA, while and display a binding specificity to the G/C and A/T rich regions, respectively. These findings were further supported by molecular docking. The cellular uptake studies suggested that was deposited mostly in the membrane fraction of the cells. Among the present complexes, exhibited a very strong cytotoxic effect on A549, MCF-7, HT-29 and DU-145 cancer cells, being more potent than cisplatin. Moreover, induces cell death through the apoptotic mode obtained by flow cytometry.
Department of Chemistry, Faculty of Arts and Sciences, Uludag University, 16059 Bursa, Turkey. vtyilmaz@uludag.edu.tr.
Veysel T
VT
Yilmaz
Department of Chemistry, Faculty of Arts and Sciences, Uludag University, 16059 Bursa, Turkey. vtyilmaz@uludag.edu.tr.
Ceyda
C
Icsel
Department of Chemistry, Faculty of Arts and Sciences, Uludag University, 16059 Bursa, Turkey. vtyilmaz@uludag.edu.tr.
Feruza
F
Suyunova
Department of Physics, Faculty of Sciences, Dokuz Eylul University, 35210 Izmir, Turkey.
Muhittin
M
Aygun
Department of Biology, Faculty of Arts and Sciences, Uludag University, 16059 Bursa, Turkey.
Nazlihan
N
Aztopal
Department of Medical Biochemistry, Medical School, Uludag University, 16059 Bursa, Turkey.
Engin
E
Ulukaya
D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives* / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001463:Barbiturates / Q000737:chemistry*; D016923:Cell Death / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004247:DNA / Q000378:metabolism; D006801:Humans; D007364:Intercalating Agents / Q000378:metabolism; D062105:Molecular Docking Simulation; D009532:Nickel / Q000737:chemistry*; D010618:Phenanthrolines / Q000737:chemistry*; D012710:Serum Albumin, Bovine / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015032:Zinc / Q000737:chemistry*
D000970:Antineoplastic Agents; D001463:Barbiturates; D056831:Coordination Complexes; D007364:Intercalating Agents; D010618:Phenanthrolines; D012710:Serum Albumin, Bovine; D015082:2,2'-Dipyridyl; D003300:Copper; D009532:Nickel; D004247:DNA; D015032:Zinc; D002945:Cisplatin; C025205:1,10-phenanthroline; C032232:barbituric acid; C048062:2,2'-dipyridylamine