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Complexes of Co (II) and Cu (II) with nonsteroidal anticancer drug Letrozole and their interaction with DNA and BSA by spectroscopic methods and cytotoxic activity

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Abstract

DNA and BSA binding properties of mononuclear Co (II) and Cu (II) complexes containing letrozole [M(Le)4Cl2]·(H2O)](Le=[4,4-(1H-1,2,4-triazol-1-ylmethylene)bisbenzonitrile] have been investigated under physiological conditions. The interaction ability of the two complexes with native calf thymus DNA(CT-DNA) has been monitored as a function of the metal complex-DNA molar ratio by UV–Vis absorption spectrophotometry, fluorescence spectroscopy, circular dichroism(CD) and thermal denaturation studies. The intrinsic binding constants, Kb, of complexes 1 and 2 with CT-DNA, obtained from UV–Vis absorption studies, were 3.15 ± 0.02 × 104 and 4.37 ± 0.02 × 104 M−1, respectively. The addition of the complexes to CT-DNA (1:2) leads to an increase in the melting temperature of DNA up to around 4 °C, which has revealed that complexes could interact with DNA through intercalation mode. Fluorimetric studies have been performed using methylene blue (MB) as a fluorescence probe and competitive studies have shown the ability of the complexes to displace the DNA-bound MB, suggesting competition with MB. To explore the potential biological value of the complexes, the binding interaction between Co (II) and Cu (II) complexes and bovine serum albumin (BSA) has also been studied by fluorescence spectroscopy. The results indicate that the reaction between the complexes and BSA is a static quenching procedure. The site marker displacement experiment has suggested the location of the complexes binding to BSA at Sudlow’s site I in subdomain IIA. Finally, MTT assay studies have shown that the bioactive complexes exert significantly high selective dose-dependent cytotoxicity against a panel of cancer cell lines including MCF-7, JURKAT, SKOV3 and U87.

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Acknowledgments

Financial support provided during this work by Islamic Azad University, Science & Research Branch, Tehran, Iran, and the Institute of Biochemistry and Biophysics University of Tehran is gratefully acknowledged.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Science, Islamic Azad University, Science and Research Branch, Tehran, Iran

    F. Tavakolyanpour, S. Waqif Husain, M. Saber Tehrani & P. Abroomand Azar

  2. Food and Drug Control Reference Laboratories, 408 Valiasr Street, Tehran, Iran

    M. H. Rastegar

  3. Department of Medical Biotechnology, Nanotechnology Research Center, School of Medicine, Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran

    A. A. Momtazi Borojeni

  4. Department of Immunology and Allergy, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    S. Alireza Esmaeili

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  1. F. Tavakolyanpour
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Tavakolyanpour, F., Waqif Husain, S., Rastegar, M.H. et al. Complexes of Co (II) and Cu (II) with nonsteroidal anticancer drug Letrozole and their interaction with DNA and BSA by spectroscopic methods and cytotoxic activity. J IRAN CHEM SOC 13, 2121–2133 (2016). https://doi.org/10.1007/s13738-016-0930-y

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