Computational screening of chalcones acting against topoisomerase IIα and their cytotoxicity towards cancer cell lines

© 2018, © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. Targeted cancer therapy has become one of the high potential cancer treatments. Human topoisomerase II (hTopoII), which catalyzes the cleavage and rejoining of double-stranded DNA, is an important...

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Main Authors: Kanyani Sangpheak, Monika Mueller, Nitchakan Darai, Peter Wolschann, Chonticha Suwattanasophon, Ritbey Ruga, Warinthon Chavasiri, Supaporn Seetaha, Kiattawee Choowongkomon, Nawee Kungwan, Chompoonut Rungnim, Thanyada Rungrotmongkol
Format: Journal
Published: 2018
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http://cmuir.cmu.ac.th/jspui/handle/6653943832/62944
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spelling th-cmuir.6653943832-629442018-12-14T03:41:56Z Computational screening of chalcones acting against topoisomerase IIα and their cytotoxicity towards cancer cell lines Kanyani Sangpheak Monika Mueller Nitchakan Darai Peter Wolschann Chonticha Suwattanasophon Ritbey Ruga Warinthon Chavasiri Supaporn Seetaha Kiattawee Choowongkomon Nawee Kungwan Chompoonut Rungnim Thanyada Rungrotmongkol Pharmacology, Toxicology and Pharmaceutics © 2018, © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. Targeted cancer therapy has become one of the high potential cancer treatments. Human topoisomerase II (hTopoII), which catalyzes the cleavage and rejoining of double-stranded DNA, is an important molecular target for the development of novel cancer therapeutics. In order to diversify the pharmacological activity of chalcones and to extend the scaffold of topoisomerase inhibitors, a series of chalcones was screened against hTopoIIα by computational techniques, and subsequently tested for their in vitro cytotoxicity. From the experimental IC50 values, chalcone 3d showed a high cytotoxicity with IC50 values of 10.8, 3.2 and 21.1 µM against the HT-1376, HeLa and MCF-7 cancer-derived cell lines, respectively, and also exhibited an inhibitory activity against hTopoIIα-ATPase that was better than the known inhibitor, salvicine. The observed ligand–protein interactions from a molecular dynamics study affirmed that 3d strongly interacts with the ATP-binding pocket residues. Altogether, the newly synthesised chalcone 3d has a high potential to serve as a lead compound for topoisomerase inhibitors. 2018-12-14T03:41:56Z 2018-12-14T03:41:56Z 2019-01-01 Journal 14756374 14756366 2-s2.0-85056085391 10.1080/14756366.2018.1507029 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85056085391&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/62944
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
topic Pharmacology, Toxicology and Pharmaceutics
spellingShingle Pharmacology, Toxicology and Pharmaceutics
Kanyani Sangpheak
Monika Mueller
Nitchakan Darai
Peter Wolschann
Chonticha Suwattanasophon
Ritbey Ruga
Warinthon Chavasiri
Supaporn Seetaha
Kiattawee Choowongkomon
Nawee Kungwan
Chompoonut Rungnim
Thanyada Rungrotmongkol
Computational screening of chalcones acting against topoisomerase IIα and their cytotoxicity towards cancer cell lines
description © 2018, © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. Targeted cancer therapy has become one of the high potential cancer treatments. Human topoisomerase II (hTopoII), which catalyzes the cleavage and rejoining of double-stranded DNA, is an important molecular target for the development of novel cancer therapeutics. In order to diversify the pharmacological activity of chalcones and to extend the scaffold of topoisomerase inhibitors, a series of chalcones was screened against hTopoIIα by computational techniques, and subsequently tested for their in vitro cytotoxicity. From the experimental IC50 values, chalcone 3d showed a high cytotoxicity with IC50 values of 10.8, 3.2 and 21.1 µM against the HT-1376, HeLa and MCF-7 cancer-derived cell lines, respectively, and also exhibited an inhibitory activity against hTopoIIα-ATPase that was better than the known inhibitor, salvicine. The observed ligand–protein interactions from a molecular dynamics study affirmed that 3d strongly interacts with the ATP-binding pocket residues. Altogether, the newly synthesised chalcone 3d has a high potential to serve as a lead compound for topoisomerase inhibitors.
format Journal
author Kanyani Sangpheak
Monika Mueller
Nitchakan Darai
Peter Wolschann
Chonticha Suwattanasophon
Ritbey Ruga
Warinthon Chavasiri
Supaporn Seetaha
Kiattawee Choowongkomon
Nawee Kungwan
Chompoonut Rungnim
Thanyada Rungrotmongkol
author_facet Kanyani Sangpheak
Monika Mueller
Nitchakan Darai
Peter Wolschann
Chonticha Suwattanasophon
Ritbey Ruga
Warinthon Chavasiri
Supaporn Seetaha
Kiattawee Choowongkomon
Nawee Kungwan
Chompoonut Rungnim
Thanyada Rungrotmongkol
author_sort Kanyani Sangpheak
title Computational screening of chalcones acting against topoisomerase IIα and their cytotoxicity towards cancer cell lines
title_short Computational screening of chalcones acting against topoisomerase IIα and their cytotoxicity towards cancer cell lines
title_full Computational screening of chalcones acting against topoisomerase IIα and their cytotoxicity towards cancer cell lines
title_fullStr Computational screening of chalcones acting against topoisomerase IIα and their cytotoxicity towards cancer cell lines
title_full_unstemmed Computational screening of chalcones acting against topoisomerase IIα and their cytotoxicity towards cancer cell lines
title_sort computational screening of chalcones acting against topoisomerase iiα and their cytotoxicity towards cancer cell lines
publishDate 2018
url https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85056085391&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/62944
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