Synthesis of Novel Hybrids of Quinazoline and Artemisinin with High Activities against Plasmodium falciparum, Human Cytomegalovirus, and Leukemia Cells
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Tony Froehlich
- Christoph Reiter
- Mohammad M Ibrahim
- Jannis Beutel
- Corina Hutterer
- Isabel Zeittraeger
- Hanife Bahsi
- Maria Leidenberger
- Oliver Friedrich
- Barbara Kappes
- Thomas Efferth
- Manfred Marschall
- Svetlana B Tsogoeva
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000406385100005&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1021/acsomega.7b00310
- Externe Identifier
- Clarivate Analytics Document Solution ID: FB8JK
- PubMed Identifier: 30023664
- ISSN
- 2470-1343
- Ausgabe der Veröffentlichung
- 6
- Zeitschrift
- ACS OMEGA
- Paginierung
- 2422 - 2431
- Datum der Veröffentlichung
- 2017
- Status
- Published
- Titel
- Synthesis of Novel Hybrids of Quinazoline and Artemisinin with High Activities against <i>Plasmodium falciparum</i>, Human Cytomegalovirus, and Leukemia Cells
- Sub types
- Article
- Ausgabe der Zeitschrift
- 2
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Autoren
- Tony Fröhlich
- Christoph Reiter
- Mohammad M Ibrahim
- Jannis Beutel
- Corina Hutterer
- Isabel Zeitträger
- Hanife Bahsi
- Maria Leidenberger
- Oliver Friedrich
- Barbara Kappes
- Thomas Efferth
- Manfred Marschall
- Svetlana B Tsogoeva
- DOI
- 10.1021/acsomega.7b00310
- eISSN
- 2470-1343
- ISSN
- 2470-1343
- Ausgabe der Veröffentlichung
- 6
- Zeitschrift
- ACS Omega
- Sprache
- en
- Online publication date
- 2017
- Paginierung
- 2422 - 2431
- Datum der Veröffentlichung
- 2017
- Status
- Published
- Herausgeber
- American Chemical Society (ACS)
- Herausgeber URL
- http://dx.doi.org/10.1021/acsomega.7b00310
- Datum der Datenerfassung
- 2023
- Titel
- Synthesis of Novel Hybrids of Quinazoline and Artemisinin with High Activities against <i>Plasmodium falciparum</i>, Human Cytomegalovirus, and Leukemia Cells
- Ausgabe der Zeitschrift
- 2
Data source: Crossref
- Abstract
- Many quinazoline derivatives have been synthesized over the last few decades with great pharmacological potential, such as antimalarial, anti-inflammatory, antimicrobial, anticancer, and antiviral. But so far, no quinazoline-artemisinin hybrids have been reported in the literature. In the present study, five novel quinazoline-artemisinin hybrids were synthesized and evaluated for their in vitro biological activity against malarial parasites (<i>Plasmodium falciparum</i> 3D7), leukemia cells (CCRF-CEM and CEM/ADR5000), and human cytomegalovirus. Remarkably, hybrid <b>9</b> (EC<sub>50</sub> = 1.4 nM), the most active antimalarial compound of this study, was not only more potent than artesunic acid (EC<sub>50</sub> = 9.7 nM) but at the same time more active than the clinically used drugs dihydroartemisinin (EC<sub>50</sub> = 2.4 nM) and chloroquine (EC<sub>50</sub> = 9.8 nM). Furthermore, hybrids <b>9</b> and <b>10</b> were the most potent compounds with regard to anticytomegaloviral activity (EC<sub>50</sub> = 0.15-0.21 μM). They were able to outperform ganciclovir (EC<sub>50</sub> = 2.6 μM), which is the relevant standard drug of antiviral therapy, by a factor of 12-17. Moreover, we identified a new highly active quinazoline derivative, compound <b>14</b>, that is most effective in suppressing cytomegalovirus replication with an EC<sub>50</sub> value in the nanomolar range (EC<sub>50</sub> = 50 nM). In addition, hybrid <b>9</b> exhibited an antileukemia effect similar to that of artesunic acid, with EC<sub>50</sub> values in the low micromolar range, and was 45 times more active toward the multidrug-resistant CEM/ADR5000 cells (EC<sub>50</sub> = 0.5 μM) than the standard drug doxorubicin.
- Addresses
- Organic Chemistry Chair I and Interdisciplinary Center for Molecular Materials (ICMM), Friedrich-Alexander University of Erlangen-Nürnberg, Henkestraße 42, 91054 Erlangen, Germany.
- Autoren
- Tony Fröhlich
- Christoph Reiter
- Mohammad M Ibrahim
- Jannis Beutel
- Corina Hutterer
- Isabel Zeitträger
- Hanife Bahsi
- Maria Leidenberger
- Oliver Friedrich
- Barbara Kappes
- Thomas Efferth
- Thomas Efferth
- Manfred Marschall
- Svetlana B Tsogoeva
- DOI
- 10.1021/acsomega.7b00310
- eISSN
- 2470-1343
- Externe Identifier
- PubMed Identifier: 30023664
- PubMed Central ID: PMC6044832
- Funding acknowledgements
- Friedrich-Alexander-Universit?t Erlangen-N?rnberg:
- Wilhelm Sander-Stiftung: 2011.085.2
- Deutsche Forschungsgemeinschaft: MM 1289/7-1/7-3
- Wilhelm Sander-Stiftung: 2014.019.1
- Bayerische Forschungsstiftung: I1/M.M.-C.H.
- Interdisciplinary Center for Molecular Materials, Friedrich-Alexander University of Erlangen-N?rnberg:
- Deutscher Akademischer Austauschdienst:
- Deutsche Forschungsgemeinschaft: TS 87/16-3
- Open access
- true
- ISSN
- 2470-1343
- Ausgabe der Veröffentlichung
- 6
- Zeitschrift
- ACS omega
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2017
- Open access status
- Open Access
- Paginierung
- 2422 - 2431
- Datum der Veröffentlichung
- 2017
- Status
- Published
- Datum der Datenerfassung
- 2018
- Titel
- Synthesis of Novel Hybrids of Quinazoline and Artemisinin with High Activities against <i>Plasmodium falciparum</i>, Human Cytomegalovirus, and Leukemia Cells.
- Sub types
- research-article
- Journal Article
- Ausgabe der Zeitschrift
- 2
Files
https://pubs.acs.org/doi/pdf/10.1021/acsomega.7b00310 https://europepmc.org/articles/PMC6044832?pdf=render
Data source: Europe PubMed Central
- Abstract
- Many quinazoline derivatives have been synthesized over the last few decades with great pharmacological potential, such as antimalarial, anti-inflammatory, antimicrobial, anticancer, and antiviral. But so far, no quinazoline-artemisinin hybrids have been reported in the literature. In the present study, five novel quinazoline-artemisinin hybrids were synthesized and evaluated for their in vitro biological activity against malarial parasites (Plasmodium falciparum 3D7), leukemia cells (CCRF-CEM and CEM/ADR5000), and human cytomegalovirus. Remarkably, hybrid 9 (EC50 = 1.4 nM), the most active antimalarial compound of this study, was not only more potent than artesunic acid (EC50 = 9.7 nM) but at the same time more active than the clinically used drugs dihydroartemisinin (EC50 = 2.4 nM) and chloroquine (EC50 = 9.8 nM). Furthermore, hybrids 9 and 10 were the most potent compounds with regard to anticytomegaloviral activity (EC50 = 0.15-0.21 μM). They were able to outperform ganciclovir (EC50 = 2.6 μM), which is the relevant standard drug of antiviral therapy, by a factor of 12-17. Moreover, we identified a new highly active quinazoline derivative, compound 14, that is most effective in suppressing cytomegalovirus replication with an EC50 value in the nanomolar range (EC50 = 50 nM). In addition, hybrid 9 exhibited an antileukemia effect similar to that of artesunic acid, with EC50 values in the low micromolar range, and was 45 times more active toward the multidrug-resistant CEM/ADR5000 cells (EC50 = 0.5 μM) than the standard drug doxorubicin.
- Date of acceptance
- 2017
- Autoren
- Tony Fröhlich
- Christoph Reiter
- Mohammad M Ibrahim
- Jannis Beutel
- Corina Hutterer
- Isabel Zeitträger
- Hanife Bahsi
- Maria Leidenberger
- Oliver Friedrich
- Barbara Kappes
- Thomas Efferth
- Manfred Marschall
- Svetlana B Tsogoeva
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/30023664
- DOI
- 10.1021/acsomega.7b00310
- Externe Identifier
- PubMed Central ID: PMC6044832
- ISSN
- 2470-1343
- Ausgabe der Veröffentlichung
- 6
- Zeitschrift
- ACS Omega
- Sprache
- eng
- Country
- United States
- Paginierung
- 2422 - 2431
- Datum der Veröffentlichung
- 2017
- Status
- Published
- Titel
- Synthesis of Novel Hybrids of Quinazoline and Artemisinin with High Activities against Plasmodium falciparum, Human Cytomegalovirus, and Leukemia Cells.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 2
Data source: PubMed
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- Property of