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 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 × 10³ M⁻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.
Quantum Optics and Photon Physics, National Physical Laboratory-Council of Scientific and Industrial Research, Dr. K.S. Krishnan Road, New Delhi 110012, India.
Sonika
S
Charak
Manish
M
Shandilya
Gunjan
G
Tyagi
Ranjana
R
Mehrotra
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism*; D001483:Base Sequence; D002417:Cattle; D002699:Chlorambucil / Q000737:chemistry / Q000378:metabolism*; D059371:DNA, B-Form / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D062105:Molecular Docking Simulation; D009690:Nucleic Acid Conformation; D010710:Phosphates / Q000378:metabolism; D013057:Spectrum Analysis
D000970:Antineoplastic Agents; D059371:DNA, B-Form; D010710:Phosphates; D002699:Chlorambucil