Spectroscopic and molecular docking studies on chlorambucil interaction with DNA

Chlorambucil (CMB) is an anticancer drug used for the treatment of variety of cancers. Structural and conformational changes associated with DNA after binding with CMB were explored using spectroscopic techniques to get insight into the mechanism of action of CMB at molecular level. Different molar...

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Bibliographic Details
Published in:International journal of biological macromolecules 2012-11, Vol.51 (4), p.406-411
Main Authors: Charak, Sonika, Shandilya, Manish, Tyagi, Gunjan, Mehrotra, Ranjana
Format: Article
Language:English
Subjects:
Animals
antineoplastic agents
Antineoplastic Agents - chemistry
Antineoplastic Agents - metabolism
Antitumor agents
Base Sequence
binding sites
Cancer
Cattle
Chlorambucil
Chlorambucil - chemistry
Chlorambucil - metabolism
Circular dichroism spectroscopy
Conformation
Cytosine
DNA
DNA, B-Form - chemistry
DNA, B-Form - genetics
DNA, B-Form - metabolism
Fourier transform infrared spectroscopy
FTIR spectroscopy
Guanine
I.R. spectroscopy
Macromolecules
mechanism of action
Molecular docking
Molecular Docking Simulation
molecular models
Nucleic Acid Conformation
Phosphates - metabolism
Spectroscopy
Spectrum Analysis
Thymine
ultraviolet-visible spectroscopy
UV–visible spectroscopy
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Summary:Chlorambucil (CMB) is an anticancer drug used for the treatment of variety of cancers. Structural and conformational changes associated with DNA after binding with CMB were explored using spectroscopic techniques to get insight into the mechanism of action of CMB at molecular level. Different molar ratios of CMB–DNA complex were prepared with constant DNA concentration under physiological conditions. FTIR spectroscopy, UV–visible spectroscopy, CD spectroscopy and molecular docking studies were employed to determine the binding site and binding constant of CMB with DNA. The results show CMB binds DNA through nitrogenous bases (thymine, guanine and cytosine). The binding constant was calculated to be 1.3×103M−1, which suggests weak binding of CMB with DNA double helix. FTIR and CD results show that CMB do not disturb native B-conformation of DNA and it continues to remain in its B conformation even at higher concentrations of CMB. The molecular docking results are in corroboration with our experimental results and provides structural insight into the interaction site.
ISSN:0141-8130
1879-0003
DOI:10.1016/j.ijbiomac.2012.06.012