Jangir, Deepak Kumar and Dey, Sanjay Kumar and Kundu, Suman and Mehrotra, Ranjana (2012) Assessment of amsacrine binding with DNA using UV-visible, circular dichroism and Raman spectroscopic techniques. Journal of Photochemistry and Photobiology B: Biology, 114. pp. 38-43. ISSN 1011-1344

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Abstract

Proper understanding of the mechanism of binding of drugs to their targets in cell is a fundamental requirement to develop new drug therapy regimen. Amsacrine is a rationally designed anticancer drug, used to treat leukemia and lymphoma. Binding with cellular DNA is a crucial step in its mechanism of cytotoxicity. Despite numerous studies, DNA binding properties of amsacrine are poorly understood. Its reversible binding with DNA does not permit X-ray crystallography or NMR spectroscopic evaluation of amsacrine-DNA complexes. In the present work, interaction of amsacrine with calf thymus DNA is investigated at physiological conditions. UV-visible, FT-Raman and circular dichroism spectroscopic techniques were employed to determine the binding mode, binding constant, sequence specificity and conformational effects of amsacrine binding to native calf thymus DNA. Our results illustrate that amsacrine interacts with DNA by and large through intercalation between base pairs. Binding constant of the amsacrine-DNA complex was found to be K = 1.2 +/- 0.1 x 10(4) M-1 which is indicative of moderate type of binding of amsacrine to DNA. Raman spectroscopic results suggest that amsacrine has a binding preference of intercalation between AT base pairs of DNA. Minor groove binding is also observed in amsacrine-DNA complexes. These results are in good agreement with in silico investigation of amsacrine binding to DNA and thus provide detailed insight into DNA binding properties of amsacrine, which could ultimately, renders its cytotoxic efficacy.

Item Type:	Article
Additional Information:	Copyright for this article belongs to M/s Elsevier.
Subjects:	Biochemistry & Molecular Biology Biophysics
Divisions:	UNSPECIFIED
Depositing User:	Users 27 not found.
Date Deposited:	06 Feb 2020 07:00
Last Modified:	06 Feb 2020 07:00
URI:	http://npl.csircentral.net/id/eprint/3687

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