Details

Autor(en) / Beteiligte

• Loganathan, Rangasamy
• Ganeshpandian, Mani
• Bhuvanesh, Nattamai S.P.
• Palaniandavar, Mallayan
• Muruganantham, Amsaveni
• Ghosh, Swapan K.
• Riyasdeen, Anvarbatcha
• Akbarsha, Mohammad Abdulkader

Titel

DNA and protein binding, double-strand DNA cleavage and cytotoxicity of mixed ligand copper(II) complexes of the antibacterial drug nalidixic acid

Ist Teil von

• Journal of inorganic biochemistry, 2017-09, Vol.174, p.1-13

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2017

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• The water soluble mixed ligand complexes [Cu(nal)(diimine)(H2O)](ClO4) 1–4, where H(nal) is nalidixic acid and diimine is 2,2′-bipyridine (1), 1,10-phenanthroline (2), 5,6-dimethyl-1,10-phenanthroline (3), and 3,4,7,8-tetramethyl-1,10-phenanthroline (4), have been isolated. The coordination geometry around Cu(II) in 1 and that in the Density Functional Theory optimized structures of 1–4 has been assessed as square pyramidal. The trend in DNA binding constants (Kb) determined using absorption spectral titration (Kb: 1, 0.79±0.1<2, 1.06±0.1<3, 1.79±0.2<4, 1.84±0.2×105M−1) is in line with that (Kapp) determined by competitive ethidium bromide binding studies. The large red-shift (10nm) observed for 2 suggests that the phen co-ligand is stacked with a frayed DNA base pair. In contrast, 3 and 4 are involved in intimate hydrophobic interaction with DNA through the methyl substituents on phen ring, which is supported by viscosity and protein binding studies. DNA docking studies imply that 4 is involved preferentially in DNA major groove binding while 1–3 in minor groove binding and that all the complexes, upon removing the axially coordinated water molecule, bind in the major groove. Interestingly, 3 and 4 display prominent double-strand DNA cleavage while 1 and 2 effect only single-strand DNA cleavage in the absence of an activator. The complexes 3 and 4 show cytotoxicity higher than 1 and 2 against human breast cancer cell lines (MCF-7). The complex 4 induces apoptotic mode of cell death in cancer cells. The complexes [Cu(nal)(diimine)(H2O)]+ [H(nal)=nalidixic acid, diimine=2,2′-bipyridine, 1,10-phenanthroline, 5,6-dimethyl-1,10-phenanthroline] bind to DNA in minor groove while [Cu(nal)(3,4,7,8-tmp)(H2O)]+ [3,4,7,8-tmp=3,4,7,8-tetramethyl-1,10-phenanthroline] binds in the major groove. The latter shows self-activated double-strand DNA cleavage and causes apoptotic cell death on MCF-7 cancer cells with potency higher than its analogues. [Display omitted] •Water soluble complexes [Cu(nal)(diimine)(H2O)]+ [H(nal)=nalidixic acid] are isolated•When diimine is 1,10-phenanthroline, it is stacked with frayed DNA base pairs•The 3,4,7,8-tetramethyl-1,10-phenanthroline complex is bound in the DNA major groove•The 3,4,7,8-tetramethyl-1,10-phenanthroline complex shows double-strand DNA cleavage•All the complexes exhibit cytotoxicity with potency higher than cisplatin