Inhibition of DNA Topoisomerase Type IIα (TOP2A) by Mitoxantrone and Its Halogenated Derivatives: A Combined Density Functional and Molecular Docking Study

doi:10.1155/2016/6817502

. 2016:2016:6817502.

doi: 10.1155/2016/6817502. Epub 2016 Feb 15.

Inhibition of DNA Topoisomerase Type IIα (TOP2A) by Mitoxantrone and Its Halogenated Derivatives: A Combined Density Functional and Molecular Docking Study

Md Abu Saleh¹, Md Solayman¹, Mohammad Mazharol Hoque², Mohammad A K Khan³, Mohammed G Sarwar⁴, Mohammad A Halim⁵

Affiliations

¹ Bangladesh Institute of Computational Chemistry and Biochemistry, 38 Green Road West, Dhaka 1205, Bangladesh; Department of Biochemistry and Molecular Biology, Jahangirnagar University, Dhaka 1342, Bangladesh.
² Bangladesh Institute of Computational Chemistry and Biochemistry, 38 Green Road West, Dhaka 1205, Bangladesh.
³ Jubail University College, Department of General Studies, Jubail 31961, Saudi Arabia.
⁴ Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, MB26, La Jolla, CA 92037, USA.
⁵ Bangladesh Institute of Computational Chemistry and Biochemistry, 38 Green Road West, Dhaka 1205, Bangladesh; Institut Lumière Matière, Université Lyon 1-CNRS, Université de Lyon, 69622 Villeurbanne Cedex, France.

PMID: 27088089
PMCID: PMC4754470
DOI: 10.1155/2016/6817502

Inhibition of DNA Topoisomerase Type IIα (TOP2A) by Mitoxantrone and Its Halogenated Derivatives: A Combined Density Functional and Molecular Docking Study

Md Abu Saleh et al. Biomed Res Int. 2016.

. 2016:2016:6817502.

doi: 10.1155/2016/6817502. Epub 2016 Feb 15.

Authors

Md Abu Saleh¹, Md Solayman¹, Mohammad Mazharol Hoque², Mohammad A K Khan³, Mohammed G Sarwar⁴, Mohammad A Halim⁵

Affiliations

¹ Bangladesh Institute of Computational Chemistry and Biochemistry, 38 Green Road West, Dhaka 1205, Bangladesh; Department of Biochemistry and Molecular Biology, Jahangirnagar University, Dhaka 1342, Bangladesh.
² Bangladesh Institute of Computational Chemistry and Biochemistry, 38 Green Road West, Dhaka 1205, Bangladesh.
³ Jubail University College, Department of General Studies, Jubail 31961, Saudi Arabia.
⁴ Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, MB26, La Jolla, CA 92037, USA.
⁵ Bangladesh Institute of Computational Chemistry and Biochemistry, 38 Green Road West, Dhaka 1205, Bangladesh; Institut Lumière Matière, Université Lyon 1-CNRS, Université de Lyon, 69622 Villeurbanne Cedex, France.

PMID: 27088089
PMCID: PMC4754470
DOI: 10.1155/2016/6817502

Abstract

In this study, mitoxantrone and its halogenated derivatives have been designed by density functional theory (DFT) to explore their structural and thermodynamical properties. The performance of these drugs was also evaluated to inhibit DNA topoisomerase type IIα (TOP2A) by molecular docking calculation. Noncovalent interactions play significant role in improving the performance of halogenated drugs. The combined quantum and molecular mechanics calculations revealed that CF3 containing drug shows better preference in inhibiting the TOP2A compared to other modified drugs.

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Figures

**Figure 1**
Optimized structure of mitoxantrone (D) and its halogenated derivatives (D1, D2, D3, D4, D5, D6, D7, D8, D9, and D10) calculated at B3LYP/MidiX level of theory.

**Figure 2**
Nonbonding interaction of D, D4, D9, and D10 with TOP2A.

**Figure 3**
D, D4, D9, and D10 interactions with surrounding residues of TOP2A generated by LigPlus.

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References

1. Gibbs J. B. Mechanism-based target identification and drug discovery in cancer research. Science. 2000;287(5460):1969–1973. doi: 10.1126/science.287.5460.1969. - DOI - PubMed
1. Yadav D. K., Khan F. QSAR, docking and ADMET studies of camptothecin derivatives as inhibitors of DNA topoisomerase-I. Journal of Chemometrics. 2013;27(1-2):21–33. doi: 10.1002/cem.2488. - DOI
1. Braña M. F., Cacho M., Gradillas A., De Pascual-Teresa B., Ramos A. Intercalators as anticancer drugs. Current Pharmaceutical Design. 2001;7(17):1745–1780. doi: 10.2174/1381612013397113. - DOI - PubMed
1. Burns C. P., Haugstad B. N., North J. A. Membrane transport of mitoxantrone by L1210 leukemia cells. Biochemical Pharmacology. 1987;36(6):857–860. doi: 10.1016/0006-2952(87)90176-6. - DOI - PubMed
1. Christmann-Franck S., Bertrand H.-O., Goupil-Lamy A., et al. Structure-based virtual screening: an application to human topoisomerase II α . Journal of Medicinal Chemistry. 2004;47(27):6840–6853. doi: 10.1021/jm049745w. - DOI - PubMed

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[1] Gibbs J. B. Mechanism-based target identification and drug discovery in cancer research. Science. 2000;287(5460):1969–1973. doi: 10.1126/science.287.5460.1969. - DOI - PubMed

[2] Gibbs J. B. Mechanism-based target identification and drug discovery in cancer research. Science. 2000;287(5460):1969–1973. doi: 10.1126/science.287.5460.1969. - DOI - PubMed

[3] Yadav D. K., Khan F. QSAR, docking and ADMET studies of camptothecin derivatives as inhibitors of DNA topoisomerase-I. Journal of Chemometrics. 2013;27(1-2):21–33. doi: 10.1002/cem.2488. - DOI

[4] Yadav D. K., Khan F. QSAR, docking and ADMET studies of camptothecin derivatives as inhibitors of DNA topoisomerase-I. Journal of Chemometrics. 2013;27(1-2):21–33. doi: 10.1002/cem.2488. - DOI

[5] Braña M. F., Cacho M., Gradillas A., De Pascual-Teresa B., Ramos A. Intercalators as anticancer drugs. Current Pharmaceutical Design. 2001;7(17):1745–1780. doi: 10.2174/1381612013397113. - DOI - PubMed

[6] Braña M. F., Cacho M., Gradillas A., De Pascual-Teresa B., Ramos A. Intercalators as anticancer drugs. Current Pharmaceutical Design. 2001;7(17):1745–1780. doi: 10.2174/1381612013397113. - DOI - PubMed

[7] Burns C. P., Haugstad B. N., North J. A. Membrane transport of mitoxantrone by L1210 leukemia cells. Biochemical Pharmacology. 1987;36(6):857–860. doi: 10.1016/0006-2952(87)90176-6. - DOI - PubMed

[8] Burns C. P., Haugstad B. N., North J. A. Membrane transport of mitoxantrone by L1210 leukemia cells. Biochemical Pharmacology. 1987;36(6):857–860. doi: 10.1016/0006-2952(87)90176-6. - DOI - PubMed

[9] Christmann-Franck S., Bertrand H.-O., Goupil-Lamy A., et al. Structure-based virtual screening: an application to human topoisomerase II α . Journal of Medicinal Chemistry. 2004;47(27):6840–6853. doi: 10.1021/jm049745w. - DOI - PubMed

[10] Christmann-Franck S., Bertrand H.-O., Goupil-Lamy A., et al. Structure-based virtual screening: an application to human topoisomerase II α . Journal of Medicinal Chemistry. 2004;47(27):6840–6853. doi: 10.1021/jm049745w. - DOI - PubMed

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Inhibition of DNA Topoisomerase Type IIα (TOP2A) by Mitoxantrone and Its Halogenated Derivatives: A Combined Density Functional and Molecular Docking Study

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Inhibition of DNA Topoisomerase Type IIα (TOP2A) by Mitoxantrone and Its Halogenated Derivatives: A Combined Density Functional and Molecular Docking Study

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