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

Md Abu Saleh; Md Solayman; Mohammad Mazharol Hoque; Mohammad A K Khan; Mohammed G Sarwar; Mohammad A Halim

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

Biomed Res Int. 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.

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.

MeSH terms

Antigens, Neoplasm / chemistry*
Binding Sites / drug effects
DNA Topoisomerases, Type II / chemistry*
DNA-Binding Proteins / antagonists & inhibitors
DNA-Binding Proteins / chemistry*
Halogenation
Humans
Mitoxantrone / analogs & derivatives
Mitoxantrone / chemistry*
Mitoxantrone / therapeutic use
Models, Molecular
Molecular Docking Simulation*
Neoplasms / drug therapy*
Poly-ADP-Ribose Binding Proteins
Quantum Theory
Thermodynamics

Substances

Antigens, Neoplasm
DNA-Binding Proteins
Poly-ADP-Ribose Binding Proteins
Mitoxantrone
DNA Topoisomerases, Type II
TOP2A protein, human