Water soluble transition metal [Ni(II), Cu(II) and Zn(II)] complexes of N -phthaloylglycinate bis(1,2-diaminocyclohexane). DNA binding, pBR322 cleavage and cytotoxicity.
Salman KhursheedHifzur R SiddiqueSartaj TabassumFarukh ArjmandPublished in: Dalton transactions (Cambridge, England : 2003) (2022)
To validate the effect of metal ions in analogous ligand scaffolds on DNA binding and cytotoxic response, we have synthesized a series of water-soluble ionic N -phthaloylglycinate conjugated bis(diaminocyclohexane)M 2+ complexes where M = Ni(II), Cu(II) and Zn(II) (1-3). The structural characterization of the complexes (1-3) was achieved by spectroscopic {FT-IR, EPR, UV-vis absorption data, 1 H NMR, ESI-MS and elemental analysis} and single crystal X-ray diffraction studies, which revealed different topologies for the late 3d-transition metals. The Ni(II) and Zn(II) complexes exhibited an octahedral geometry with coordinated labile water molecules in the P 1̄ space group while the Cu(II) complex revealed a square planar geometry with the P 2 1 / c space lattice. In vitro DNA-complexation studies were performed employing various complementary biophysical methods to quantify the intrinsic binding constant K b and K sv values and to envisage the binding modes and binding affinity of (1-3) at the therapeutic targets. The corroborative results of these experiments revealed a substantial geometric and electronic effect of (1-3) on DNA binding and the following inferences were observed, (i) high K b and K sv values, (ii) remarkable cleavage efficiency via an oxidative pathway, (iii) condensation behavior and (iv) good cytotoxic response to HepG2 and PTEN-caP8 cancer cell lines, with copper(II) complex 2 outperforming the other two complexes as a most promising anticancer drug candidate. Copper(II) complexes have been proven in the literature to be good anticancer drug entities, displaying inhibition of uncontrolled-cell growth by multiple pathways viz. , anti-angiogenesis, inducing apoptosis and reactive oxygen species mediated cell death phenomena. Nickel(II) and zinc(II) ionic complexes 1 and 3 have also demonstrated good chemotherapeutic potential in vitro and the bioactive 1,2-diaminocyclohexane fragment in these complexes plays an instrumental role in anticancer activity.
Keyphrases
- dna binding
- cell death
- transcription factor
- reactive oxygen species
- systematic review
- magnetic resonance imaging
- magnetic resonance
- ionic liquid
- machine learning
- cell proliferation
- computed tomography
- ms ms
- gold nanoparticles
- transition metal
- risk assessment
- signaling pathway
- young adults
- quantum dots
- electronic health record
- artificial intelligence
- cell cycle arrest
- anti inflammatory
- vascular endothelial growth factor
- oxide nanoparticles
- circulating tumor cells
- tissue engineering