Spectroscopic analysis of the interaction of lomustine with calf thymus DNA

作者: Shweta Agarwal , Deepak Kumar Jangir , Parul Singh , Ranjana Mehrotra

DOI: 10.1016/J.JPHOTOBIOL.2013.11.017

关键词:

摘要: Abstract Investigation of drug–DNA interaction is important for understanding the drug action at molecular level and designing specific DNA targeted drug. Lomustine (CCNU = 1-[2-chloroethyl]-3-cyclohexyl-1-nitroso-urea) an alkylating antineoplastic nitrosourea derivative, used to treat different types cancer. In present study, conformational structural effects lomustine on are investigated using spectroscopic approaches. Different drug/DNA molar ratios analyzed determine binding sites mode with DNA. Fourier transform infrared (FTIR) results suggest nitrogenous bases guanine cytosine along weak sugar-phosphate backbone Circular dichroism (CD) show perturbation in local conformation upon helix. These changes may act as recognition site enzymes that further causes alkylation Spectroscopic confirm formation intermediate stage occurs during transition B-conformation into A-conformation.

参考文章(45)
Lutz F. Tietze, Birgit Krewer, Felix Major, Ingrid Schuberth, CD-Spectroscopy As a Powerful Tool for Investigating the Mode of Action of Unmodified Drugs in Live Cells Journal of the American Chemical Society. ,vol. 131, pp. 13031- 13036 ,(2009) , 10.1021/JA902767F
Zhivko Zhelev, Rumiana Bakalova, Ichio Aoki, Ken-ichiro Matsumoto, Veselina Gadjeva, Kazunori Anzai, Iwao Kanno, Nitroxyl radicals for labeling of conventional therapeutics and noninvasive magnetic resonance imaging of their permeability for blood-brain barrier: relationship between structure, blood clearance, and MRI signal dynamic in the brain. Molecular Pharmaceutics. ,vol. 6, pp. 504- 512 ,(2009) , 10.1021/MP800175K
J M G Larkin, S A Hughes, D A Beirne, P M Patel, I M Gibbens, S C Bate, K Thomas, T G Eisen, M E Gore, A Phase I/II study of lomustine and temozolomide in patients with cerebral metastases from malignant melanoma British Journal of Cancer. ,vol. 96, pp. 44- 48 ,(2007) , 10.1038/SJ.BJC.6603503
Sonika Charak, Deepak K. Jangir, Gunjan Tyagi, Ranjana Mehrotra, Interaction studies of Epirubicin with DNA using spectroscopic techniques Journal of Molecular Structure. ,vol. 1000, pp. 150- 154 ,(2011) , 10.1016/J.MOLSTRUC.2011.06.013
Regis Marty, Christophe N N'soukpoé-Kossi, David Charbonneau, Carl Maximilian Weinert, Laurent Kreplak, Heidar-Ali Tajmir-Riahi, Structural analysis of DNA complexation with cationic lipids. Nucleic Acids Research. ,vol. 37, pp. 849- 857 ,(2009) , 10.1093/NAR/GKN1003
Tomoo Miyahara, Hiroshi Nakatsuji, Hiroshi Sugiyama, Helical structure and circular dichroism spectra of DNA: a theoretical study. Journal of Physical Chemistry A. ,vol. 117, pp. 42- 55 ,(2013) , 10.1021/JP3085556
K. Nejedl , Mapping the B-A conformational transition along plasmid DNA Nucleic Acids Research. ,vol. 33, ,(2005) , 10.1093/NAR/GNI008
Alexander M. Spence, Rodney J. Y. Ho, Russell J. Geyer, Claudette R. Bethune, Lipid association improves the therapeutic index of lomustine [1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea] to suppress 36B-10 tumor growth in rats. Cancer Research. ,vol. 61, pp. 3669- 3674 ,(2001)
Finn Drabløs, Emadoldin Feyzi, Per Arne Aas, Cathrine B. Vaagbø, Bodil Kavli, Marit S. Bratlie, Javier Peña-Diaz, Marit Otterlei, Geir Slupphaug, Hans E. Krokan, Alkylation damage in DNA and RNA--repair mechanisms and medical significance. DNA Repair. ,vol. 3, pp. 1389- 1407 ,(2004) , 10.1016/J.DNAREP.2004.05.004