Artemisinin Derivatives Target Topoisomerase 1 and Cause DNA Damage in Silico and in Vitro
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Onat Kadioglu
- Ariel Chan
- Alena Cong Ling Qiu
- Vincent Kam Wai Wong
- Vanessa Colligs
- Sabine Wecklein
- Halima Freund-Henni Rached
- Thomas Efferth
- Wen-Luan Wendy Hsiao
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000412506200001&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.3389/fphar.2017.00711
- eISSN
- 1663-9812
- Externe Identifier
- Clarivate Analytics Document Solution ID: FJ1UU
- PubMed Identifier: 29062278
- Zeitschrift
- FRONTIERS IN PHARMACOLOGY
- Schlüsselwörter
- artemisinin
- cancer
- DNA damage
- molecular docking
- topoisomerase
- Artikelnummer
- ARTN 711
- Datum der Veröffentlichung
- 2017
- Status
- Published
- Titel
- Artemisinin Derivatives Target Topoisomerase 1 and Cause DNA Damage <i>in Silico</i> and <i>in Vitro</i>
- Sub types
- Article
- Ausgabe der Zeitschrift
- 8
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Autoren
- Onat Kadioglu
- Ariel Chan
- Alena Cong Ling Qiu
- Vincent Kam Wai Wong
- Vanessa Colligs
- Sabine Wecklein
- Halima Freund-Henni Rached
- Thomas Efferth
- Wen-Luan Wendy Hsiao
- DOI
- 10.3389/fphar.2017.00711
- eISSN
- 1663-9812
- Zeitschrift
- Frontiers in Pharmacology
- Online publication date
- 2017
- Status
- Published online
- Herausgeber
- Frontiers Media SA
- Herausgeber URL
- http://dx.doi.org/10.3389/fphar.2017.00711
- Datum der Datenerfassung
- 2022
- Titel
- Artemisinin Derivatives Target Topoisomerase 1 and Cause DNA Damage in Silico and in Vitro
- Ausgabe der Zeitschrift
- 8
Data source: Crossref
- Abstract
- DNA topoisomerases 1 and 2 are enzymes that maintain DNA topology and play important essential genome functions, including DNA replication and transcription. Aberrant topoisomerases cause genome instability and a wide range of diseases, cancer in particular. Both Topo 1 and 2 are the targets of valuable anticancer drugs, such as camptothecin. It has been previously shown that artemisinin, a sesquiterpene lactone from <i>Artemisia annua</i> L. also known as <i>qinghaosu</i>, possesses anti-cancer effects and one of its derivatives, artesunate inhibits Topo 2. In this study, we evaluated artemisinin and 40 derivatives as potential Topo 1 inhibitors at first by <i>in silico</i> molecular docking analyses. Five compounds that showed comparable binding energies and similar docking poses were selected for <i>in vitro</i> cytotoxicity test and Comet assay for DNA damage. WWLL-013, WWLL-022, and WWLL-1098 showed the lowest binding energy also induced DNA damage in the Comet assay. CMK-0298 and CMK-0398 intercalated into DNA and induced mild DNA damage. All selected compounds, WWLL-013 in particular, were more cytotoxic toward the rat tumor cells than to the normal cells. In conclusion, the artemisinin derivatives such as CMK-0298, CMK-0398, WWLL-013, WWLL-022, and WWLL-1098 can be further developed as Topo 1 inhibitors.
- Addresses
- Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Mainz, Germany.
- Autoren
- Onat Kadioglu
- Ariel Chan
- Alena Cong Ling Qiu
- Vincent Kam Wai Wong
- Vanessa Colligs
- Sabine Wecklein
- Halima Freund-Henni Rached
- Thomas Efferth
- Thomas Efferth
- Wen-Luan Wendy Hsiao
- DOI
- 10.3389/fphar.2017.00711
- eISSN
- 1663-9812
- Externe Identifier
- PubMed Identifier: 29062278
- PubMed Central ID: PMC5640709
- Open access
- true
- ISSN
- 1663-9812
- Zeitschrift
- Frontiers in pharmacology
- Sprache
- eng
- Medium
- Electronic-eCollection
- Online publication date
- 2017
- Open access status
- Open Access
- Paginierung
- 711
- Datum der Veröffentlichung
- 2017
- Status
- Published
- Publisher licence
- CC BY
- Datum der Datenerfassung
- 2017
- Titel
- Artemisinin Derivatives Target Topoisomerase 1 and Cause DNA Damage <i>in Silico</i> and <i>in Vitro</i>.
- Sub types
- research-article
- Journal Article
- Ausgabe der Zeitschrift
- 8
Files
https://www.frontiersin.org/articles/10.3389/fphar.2017.00711/pdf https://europepmc.org/articles/PMC5640709?pdf=render
Data source: Europe PubMed Central
- Abstract
- DNA topoisomerases 1 and 2 are enzymes that maintain DNA topology and play important essential genome functions, including DNA replication and transcription. Aberrant topoisomerases cause genome instability and a wide range of diseases, cancer in particular. Both Topo 1 and 2 are the targets of valuable anticancer drugs, such as camptothecin. It has been previously shown that artemisinin, a sesquiterpene lactone from Artemisia annua L. also known as qinghaosu, possesses anti-cancer effects and one of its derivatives, artesunate inhibits Topo 2. In this study, we evaluated artemisinin and 40 derivatives as potential Topo 1 inhibitors at first by in silico molecular docking analyses. Five compounds that showed comparable binding energies and similar docking poses were selected for in vitro cytotoxicity test and Comet assay for DNA damage. WWLL-013, WWLL-022, and WWLL-1098 showed the lowest binding energy also induced DNA damage in the Comet assay. CMK-0298 and CMK-0398 intercalated into DNA and induced mild DNA damage. All selected compounds, WWLL-013 in particular, were more cytotoxic toward the rat tumor cells than to the normal cells. In conclusion, the artemisinin derivatives such as CMK-0298, CMK-0398, WWLL-013, WWLL-022, and WWLL-1098 can be further developed as Topo 1 inhibitors.
- Date of acceptance
- 2017
- Autoren
- Onat Kadioglu
- Ariel Chan
- Alena Cong Ling Qiu
- Vincent Kam Wai Wong
- Vanessa Colligs
- Sabine Wecklein
- Halima Freund-Henni Rached
- Thomas Efferth
- Wen-Luan Wendy Hsiao
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/29062278
- DOI
- 10.3389/fphar.2017.00711
- Externe Identifier
- PubMed Central ID: PMC5640709
- ISSN
- 1663-9812
- Zeitschrift
- Front Pharmacol
- Schlüsselwörter
- DNA damage
- artemisinin
- cancer
- molecular docking
- topoisomerase
- Sprache
- eng
- Country
- Switzerland
- Paginierung
- 711
- Datum der Veröffentlichung
- 2017
- Status
- Published online
- Titel
- Artemisinin Derivatives Target Topoisomerase 1 and Cause DNA Damage in Silico and in Vitro.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 8
Data source: PubMed
- Beziehungen:
- Property of