Publication: Molecular dynamics simulations of sulfone derivatives in complex with DNA topoisomerase IIα ATPase domain
Issued Date
2020-01-01
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ISSN
15380254
07391102
07391102
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2-s2.0-85093953831
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of Biomolecular Structure and Dynamics. (2020)
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Kanika Verma, Panupong Mahalapbutr, Atima Auepattanapong, Onnicha Khaikate, Chutima Kuhakarn, Kaito Takahashi, Thanyada Rungrotmongkol Molecular dynamics simulations of sulfone derivatives in complex with DNA topoisomerase IIα ATPase domain. Journal of Biomolecular Structure and Dynamics. (2020). doi:10.1080/07391102.2020.1831961 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/59897
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Title
Molecular dynamics simulations of sulfone derivatives in complex with DNA topoisomerase IIα ATPase domain
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Abstract
© 2020 Informa UK Limited, trading as Taylor & Francis Group. Human topoisomerase II alpha (TopoIIα) is a crucial enzyme involved in maintaining genomic integrity during the process of DNA replication and mitotic division. It is a vital therapeutic target for designing novel anticancer agents in targeted cancer therapy. Sulfones, members of organosulfur compounds, have been reported to possess various biological activities such as antimicrobial, anti-inflammatory, anti-HIV, anticancer, and antimalarial properties. In the present study, a series of sulfones was selected to evaluate their inhibitory activity against TopoIIα using computational approaches. Molecular docking results revealed that several sulfone analogs bind efficiently to the ATPase domain of TopoIIα. Among them, sulfones 18a, 60a, *4 b, *8 b, *3c, and 8c exhibit higher binding affinity than the known TopoII inhibitor, salvicine. Molecular dynamics simulations and free energy calculations based on MM/PB(GB)SA method demonstrated that sulfone *8 b strongly interacts with amino acid residues in the ATP-binding pocket (E87, N91, D94, I125, I141, F142, S149, G161, and A167), driven mainly by an electrostatic attraction and a strong H-bond formation at G161 residue. Altogether, the obtained results predicted that sulfones could have a high potential to be a lead molecule for targeting TopoIIα. Communicated by Ramaswamy H. Sarma.