-
Computational screening of chalcones acting against topoisomerase IIα and their cytotoxicity towards cancer cell lines
- Back
Metadata
Document Title
Computational screening of chalcones acting against topoisomerase IIα and their cytotoxicity towards cancer cell lines
Author
Sangpheak K.,Mueller M.,Darai N.,Wolschann P.,Suwattanasophon C.,Ruga R.,Chavasiri W.,Seetaha S.,Choowongkomon K.,Kungwan N.,Rungnim C.,Rungrotmongkol T.
Name from Authors Collection
Affiliations
Faculty of Science, Program in Biotechnology, Chulalongkorn University, Bangkok, Thailand; Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Vienna, Austria; Institute of Theoretical Chemistry, University of Vienna, Vienna, Austria; Faculty of Science, Center of Excellence in Natural Products Chemistry, Department of Chemistry, Chulalongkorn University, Bangkok, Thailand; Faculty of Science, Department of Biochemistry, Kasetsart University, Bangkok, Thailand; Faculty of Science, Department of Chemistry, Chiang Mai University, Chiang, Mai, Thailand; Center of Excellence in Materials Science and Technology, Chiang Mai University, Chiang, Mai, Thailand; Nanoscale Simulation Laboratory, National Nanotechnology Center, National Science and Technology Development Agency, Pathum Thani, Thailand; Faculty of Science, Biocatalyst and Environmental Biotechnology Research Unit, Department of Biochemistry, Chulalongkorn University, Bangkok, Thailand; Faculty of Science, Ph.D. Program in Bioinformatics and Computational Biology, Chulalongkorn University, Bangkok, Thailand
Type
Article
Source Title
Journal of Enzyme Inhibition and Medicinal Chemistry
ISSN
14756366
Year
2019
Volume
34
Issue
1
Open Access
All Open Access, Gold, Green
Publisher
Taylor and Francis Ltd
DOI
10.1080/14756366.2018.1507029
Abstract
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, © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
Industrial Classification
Knowledge Taxonomy Level 1
Knowledge Taxonomy Level 2
Knowledge Taxonomy Level 3
Funding Sponsor
Chulalongkorn University; Thailand Research Fund; Thailand Graduate Institute of Science and Technology
License
CC BY-NC
Rights
Taylor & Francis Group
Publication Source
Scopus