4.7 Article

Nuclear blebbing of biologically active organoselenium compound towards human cervical cancer cell (HeLa): In vitro DNA/HSA binding, cleavage and cell imaging studies

Journal

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 90, Issue -, Pages 876-888

Publisher

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2014.12.014

Keywords

Organoselenium compound; X-ray crystallography; DFT studies; DNA binding; pBR322 hydrolytic cleavage; GPx activity

Funding

  1. DST, University of Kashmir
  2. DST-PURSE [SR/S9/Z-23/2008/12(C)]
  3. DST-FIST programme [CSI-234/2011]
  4. DRS-I (SAP) from UGC, New Delhi, India [F.540/1/DRS/2009/(SAP-I)]
  5. CSIR-SRF (SRF scheme), New Delhi [2013: 9/112(503) 2K13-EMR-I]

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New pharmacophore organoselenium compound (1) was designed, synthesized and characterized by various spectroscopic methods (IR, ESI-MS, H-1, C-13 and Se-77 NMR) and further confirmed by X-ray crystallography. Compound 1 consists of two 3,5-bis(trifluoromethyl)phenyl units which are connected to the selenium atom via the organometallic C-Se bond. In vitro DNA binding studies of 1 was investigated by absorption and emission titration methods which revealed that I recognizes the minor groove of DNA in accordance with molecular docking studies with the DNA duplex. Gel electrophoretic assay demonstrates the ability of 1 to cleave pBR322 DNA through hydrolytic process which was further validated by T4 religation assay. To understand the drug-protein interaction of which ultimate molecular target was DNA, the affinity of 1 towards HSA was also investigated by the spectroscopic and molecular modeling techniques which showed hydrophobic interaction in the subdomain HA of HSA. Furthermore, the intracellular localization of 1 was evidenced by cell imaging studies using HeLa cells. (C) 2014 Elsevier Masson SAS. All rights reserved.

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