Molecular recognition of naphthoquinone-containing compounds against human DNA topoisomerase IIα ATPase domain: A molecular modeling study

© 2017 Elsevier B.V. Several quinone-based metabolites of anticancer drugs and naturally occurring quinone-containing compounds have been characterized as potent inhibitors toward topoisomerase IIα (TopoIIα), an essential enzyme involved in maintaining genomic integrity during DNA replication and mi...

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Main Authors: Panupong Mahalapbutr, Phakawat Chusuth, Nawee Kungwan, Warinthorn Chavasiri, Peter Wolschann, Thanyada Rungrotmongkol
Format: Journal
Published: 2018
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http://cmuir.cmu.ac.th/jspui/handle/6653943832/43442
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spelling th-cmuir.6653943832-434422018-04-25T07:35:18Z Molecular recognition of naphthoquinone-containing compounds against human DNA topoisomerase IIα ATPase domain: A molecular modeling study Panupong Mahalapbutr Phakawat Chusuth Nawee Kungwan Warinthorn Chavasiri Peter Wolschann Thanyada Rungrotmongkol Chemistry Materials Science Agricultural and Biological Sciences Arts and Humanities © 2017 Elsevier B.V. Several quinone-based metabolites of anticancer drugs and naturally occurring quinone-containing compounds have been characterized as potent inhibitors toward topoisomerase IIα (TopoIIα), an essential enzyme involved in maintaining genomic integrity during DNA replication and mitotic division. Mansonone G (MG), a naphthoquinone-containing compound extracted from the heartwood of Mansonia gagei, exhibits various biological activities including antitumor potential. In the present study, MG and its semi-synthetic derivatives were selected to study the preferential binding site and dynamics behavior as well as to predict the inhibitory activity against TopoIIα using molecular modeling approaches. The molecular docking results revealed that the entire series of MG preferentially target to the ATPase domain. Among all studied MGs, the ester derivative MG14 containing C-10 length exhibited the highest binding affinity against TopoIIα and greater than that of the ATP-competitive inhibitor salvicine as well as 1,4-benzoquinone. Interestingly, the MG14 binding could induce the closed form of the turn region (residues 147–151) inside ATP-binding pocket, implying that this event might be one of the crucial mechanisms underlying TopoIIα inhibition. The obtained theoretical information is useful as rational guide for further development of new anticancer agents containing naphthoquinone moiety against TopoIIα. 2018-01-24T03:48:36Z 2018-01-24T03:48:36Z 2017-12-01 Journal 01677322 2-s2.0-85031103516 10.1016/j.molliq.2017.10.021 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85031103516&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/43442
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
topic Chemistry
Materials Science
Agricultural and Biological Sciences
Arts and Humanities
spellingShingle Chemistry
Materials Science
Agricultural and Biological Sciences
Arts and Humanities
Panupong Mahalapbutr
Phakawat Chusuth
Nawee Kungwan
Warinthorn Chavasiri
Peter Wolschann
Thanyada Rungrotmongkol
Molecular recognition of naphthoquinone-containing compounds against human DNA topoisomerase IIα ATPase domain: A molecular modeling study
description © 2017 Elsevier B.V. Several quinone-based metabolites of anticancer drugs and naturally occurring quinone-containing compounds have been characterized as potent inhibitors toward topoisomerase IIα (TopoIIα), an essential enzyme involved in maintaining genomic integrity during DNA replication and mitotic division. Mansonone G (MG), a naphthoquinone-containing compound extracted from the heartwood of Mansonia gagei, exhibits various biological activities including antitumor potential. In the present study, MG and its semi-synthetic derivatives were selected to study the preferential binding site and dynamics behavior as well as to predict the inhibitory activity against TopoIIα using molecular modeling approaches. The molecular docking results revealed that the entire series of MG preferentially target to the ATPase domain. Among all studied MGs, the ester derivative MG14 containing C-10 length exhibited the highest binding affinity against TopoIIα and greater than that of the ATP-competitive inhibitor salvicine as well as 1,4-benzoquinone. Interestingly, the MG14 binding could induce the closed form of the turn region (residues 147–151) inside ATP-binding pocket, implying that this event might be one of the crucial mechanisms underlying TopoIIα inhibition. The obtained theoretical information is useful as rational guide for further development of new anticancer agents containing naphthoquinone moiety against TopoIIα.
format Journal
author Panupong Mahalapbutr
Phakawat Chusuth
Nawee Kungwan
Warinthorn Chavasiri
Peter Wolschann
Thanyada Rungrotmongkol
author_facet Panupong Mahalapbutr
Phakawat Chusuth
Nawee Kungwan
Warinthorn Chavasiri
Peter Wolschann
Thanyada Rungrotmongkol
author_sort Panupong Mahalapbutr
title Molecular recognition of naphthoquinone-containing compounds against human DNA topoisomerase IIα ATPase domain: A molecular modeling study
title_short Molecular recognition of naphthoquinone-containing compounds against human DNA topoisomerase IIα ATPase domain: A molecular modeling study
title_full Molecular recognition of naphthoquinone-containing compounds against human DNA topoisomerase IIα ATPase domain: A molecular modeling study
title_fullStr Molecular recognition of naphthoquinone-containing compounds against human DNA topoisomerase IIα ATPase domain: A molecular modeling study
title_full_unstemmed Molecular recognition of naphthoquinone-containing compounds against human DNA topoisomerase IIα ATPase domain: A molecular modeling study
title_sort molecular recognition of naphthoquinone-containing compounds against human dna topoisomerase iiα atpase domain: a molecular modeling study
publishDate 2018
url https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85031103516&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/43442
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