title: Spectroscopic analysis of the interaction of lomustine with calf thymus DNA.
abstract: Investigation of drug-DNA interaction is important for understanding the drug action at molecular level and for designing specific DNA targeted drug. Lomustine (CCNU=1-[2-chloroethyl]-3-cyclohexyl-1-nitroso-urea) is an alkylating antineoplastic nitrosourea derivative, used to treat different types of cancer. In the present study, conformational and structural effects of lomustine on DNA are investigated using different spectroscopic approaches. Different drug/DNA molar ratios are analyzed to determine the binding sites and binding mode of lomustine with DNA. Fourier transform infrared spectroscopic (FTIR) results suggest binding of lomustine with nitrogenous bases guanine and cytosine along with weak interaction to the sugar-phosphate backbone of DNA. Circular dichroism (CD) spectroscopic results show perturbation in the local conformation of DNA upon binding of lomustine with DNA helix. These local conformational changes may act as recognition site for alkylating enzymes that further causes alkylation of DNA. Spectroscopic results confirm the formation of an intermediate stage of DNA that occurs during the transition of B-conformation into A-conformation.
authors.affiliation: Quantum Optics and Photon Physics, CSIR-National Physical Laboratory, Dr. K.S. Krishnan Marg, New Delhi 110012, India.
authors.forename: Shweta
authors.initials: S
authors.lastname: Agarwal
authors.affiliation: Quantum Optics and Photon Physics, CSIR-National Physical Laboratory, Dr. K.S. Krishnan Marg, New Delhi 110012, India.
authors.forename: Deepak Kumar
authors.initials: DK
authors.lastname: Jangir
authors.affiliation: Quantum Optics and Photon Physics, CSIR-National Physical Laboratory, Dr. K.S. Krishnan Marg, New Delhi 110012, India.
authors.forename: Parul
authors.initials: P
authors.lastname: Singh
authors.affiliation: Quantum Optics and Photon Physics, CSIR-National Physical Laboratory, Dr. K.S. Krishnan Marg, New Delhi 110012, India. Electronic address: ranjana@mail.nplindia.ernet.in.
authors.forename: Ranjana
authors.initials: R
authors.lastname: Mehrotra
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000737:chemistry*; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D008130:Lomustine / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D018906:Antineoplastic Agents, Alkylating; D008130:Lomustine; D004247:DNA; C427203:calf thymus DNA
keywords: CD spectroscopy; Drug–DNA interaction; FTIR spectroscopy; Lomustine