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Molecular Modeling Study of Interaction of Anthracenedione Class of Drug Mitoxantrone and Its Analogs with DNA Tetrameric Sequences

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Software Tools and Algorithms for Biological Systems

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 696))

Abstract

Numbers of drugs are being synthesized every year to meet the target of safe and disease-free society. Presently molecular modeling technique is used to unfold the mechanism of action of drugs alone or in conjunction with experimental methodologies. There are a number of drugs which are successfully developed using this methodology. Mitoxantrone (MTX) – 1, 4-dihydroxy-5, 8-bis {[2-(2-hydroxyethyl) amino] amino}-9, 10-anthracenedione is marketed under the name Novantrone, an anticancer drug used in chemotherapy. Its important analog ametantrone and various other analogs differ from one another in the position of side chain or functionalities on the chromophore eventually exhibit varied biological activities. DNA binding is an important phenomenon for anticancer activity of these drugs. In order to understand the interactions of the drug molecules with its receptor site, at atomic level, we have carried out computer simulations of drug and DNA alone and also in complex mode in water as a medium. All the simulations are being carried out using molecular operating environment (MOE) and X3DNA software tools on SUN SOLARIS platform. Interaction energy of all the drug molecules with DNA is determined and compared. Also the structural changes in DNA and drug before and after complex formation are studied extensively.

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Acknowledgments

Research work reported in this manuscript is supported by the research grant under R&D, Ministry of Human Resources and Development, Government of India. The facilities provided by the NMR Centre, India Institute of Technology Roorkee (IIT-R), Uttaranchal, are highly acknowledged. (Tables 1–5 as a supplementary material.)

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  1. Department of Chemistry, National Institute of Technology, Hamirpur, Himachal Pradesh, India

    Pamita Awasthi

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  1. Pamita Awasthi
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  2. Shilpa Dogra
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  3. Lalit K. Awasthi
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  4. Ritu Barthwal
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Correspondence to Pamita Awasthi .

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Editors and Affiliations

  1. Dept. Computer Science, University of Georgia, Athens, 30602-7404, Georgia, USA

    Hamid R. Arabnia

  2. , Department of Computer Science, Lamar University, Beaumont, 77710, Texas, USA

    Quoc-Nam Tran

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Awasthi, P., Dogra, S., Awasthi, L.K., Barthwal, R. (2011). Molecular Modeling Study of Interaction of Anthracenedione Class of Drug Mitoxantrone and Its Analogs with DNA Tetrameric Sequences. In: Arabnia, H., Tran, QN. (eds) Software Tools and Algorithms for Biological Systems. Advances in Experimental Medicine and Biology, vol 696. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7046-6_39

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