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Iran J Pharm Res. 2014;13(4):1279-94.

The Effects of Extending of Co-planarity in a Series of Structurally Relative Polypyridyl Palladium(II) Complexes on DNA-binding and Cytotoxicity Properties.

Iranian journal of pharmaceutical research : IJPR

Somaye Shahraki, Hassan Mansouri-Torshizi, Ziba Sori Nezami, Arezou Ghahghaei, Fatemeh Yaghoubi, Adeleh Divsalar, Ali-Akbar Saboury, Farshad H Shirazi

Affiliations

  1. Department of Chemistry, University of Sistan & Baluchestan, Zahedan, Iran.
  2. Department of Biology, University of Sistan & Baluchestan, Zahedan, Iran.
  3. Department of Biological Sciences, Tarbiat Moallem University, Tehran, Iran.
  4. Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
  5. Pharmaceutical Sciences Research Center, Shahid Behesthi University of Medical Sciences, Tehran, Iran.

PMID: 25587317 PMCID: PMC4232794

Abstract

In depth interaction studies between calf thymus deoxyribonucleic acid (CT-DNA) and a series of four structurally relative palladium(II) complexes [Pd(en)(HB)](NO3)2 (a-d), where en is ethylenediamine and heterocyclic base (HB) is 2,2'-bipyridine (bpy, a); 1,10-phenanthroline (phen, b); dipyridoquinoxaline (dpq, c) and dipyridophenazine (dppz, d) (Figure 1), were performed. These studies have been investigated by utilizing the electronic absorption spectroscopy, fluorescence spectra and ethidium bromide (EBr) displacement and gel filtration techniques. a-d complexes cooperatively bind and denature the DNA at low concentrations. Their concentration at midpoint of transition, L1/2, follows the order a >> b > c > d. Also the g, the number of binding sites per 1000 nucleotides, follows the order a >> b ~ c > d. EBr and Scatchard experiments for a-d complexes suggest efficient intercalative binding affinity to CT-DNA giving the order: d > c > b > a. Several binding and thermodynamic parameters are also described. The biological activity of these cationic and water soluble palladium complexes were tested against chronic myelogenous leukemia cell line, K562. b, c and d complexes show cytotoxic concentration (Cc50) values much lower than cisplatin.

Keywords: Cytotoxicity; DNA binding; Pd(II) complexes

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