Synthesis of Thymoquinone-Artemisinin Hybrids: New Potent Antileukemia, Antiviral, and Antimalarial Agents
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Tony Froehlich
- Christoph Reiter
- Mohamed EM Saeed
- Corina Hutterer
- Friedrich Hahn
- Maria Leidenberger
- Oliver Friedrich
- Barbara Kappes
- Manfred Marschall
- Thomas Efferth
- Svetlana B Tsogoeva
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000435613500005&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1021/acsmedchemlett.7b00412
- Externe Identifier
- Clarivate Analytics Document Solution ID: GJ8BE
- PubMed Identifier: 29937978
- ISSN
- 1948-5875
- Ausgabe der Veröffentlichung
- 6
- Zeitschrift
- ACS MEDICINAL CHEMISTRY LETTERS
- Schlüsselwörter
- Artemisinin
- thymoquinone
- natural product hybrid
- antimalarial activity
- antiviral activity
- anticancer activity
- Paginierung
- 534 - 539
- Datum der Veröffentlichung
- 2018
- Status
- Published
- Titel
- Synthesis of Thymoquinone-Artemisinin Hybrids: New Potent Antileukemia, Antiviral, and Antimalarial Agents
- Sub types
- Article
- Ausgabe der Zeitschrift
- 9
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Autoren
- Tony Fröhlich
- Christoph Reiter
- Mohamed EM Saeed
- Corina Hutterer
- Friedrich Hahn
- Maria Leidenberger
- Oliver Friedrich
- Barbara Kappes
- Manfred Marschall
- Thomas Efferth
- Svetlana B Tsogoeva
- DOI
- 10.1021/acsmedchemlett.7b00412
- eISSN
- 1948-5875
- ISSN
- 1948-5875
- Ausgabe der Veröffentlichung
- 6
- Zeitschrift
- ACS Medicinal Chemistry Letters
- Sprache
- en
- Online publication date
- 2017
- Paginierung
- 534 - 539
- Datum der Veröffentlichung
- 2018
- Status
- Published
- Herausgeber
- American Chemical Society (ACS)
- Herausgeber URL
- http://dx.doi.org/10.1021/acsmedchemlett.7b00412
- Datum der Datenerfassung
- 2023
- Titel
- Synthesis of Thymoquinone–Artemisinin Hybrids: New Potent Antileukemia, Antiviral, and Antimalarial Agents
- Ausgabe der Zeitschrift
- 9
Data source: Crossref
- Abstract
- A series of hybrid compounds based on the natural products artemisinin and thymoquinone was synthesized and investigated for their biological activity against the malaria parasite <i>Plasmodium falciparum</i> 3D7 strain, human cytomegalovirus (HCMV), and two leukemia cell lines (drug-sensitive CCRF-CEM and multidrug-resistant subline CEM/ADR5000). An unprecedented one-pot method of selective formation of C-10α-acetate <b>14</b> starting from a 1:1 mixture of C-10α- to C-10β-dihydroartemisinin was developed. The key step of this facile method is a mild decarboxylative activation of malonic acid mediated by DCC/DMAP. Ether-linked thymoquinone-artemisinin hybrids <b>6a/b</b> stood out as the most active compounds in all categories, while showing no toxic side effects toward healthy human foreskin fibroblasts and thus being selective. They exhibited EC<sub>50</sub> values of 0.2 μM against the doxorubicin-sensitive as well as the multidrug-resistant leukemia cells and therefore can be regarded as superior to doxorubicin. Moreover, they showed to be five times more active than the standard drug ganciclovir and nearly eight times more active than artesunic acid against HCMV. In addition, hybrids <b>6a/b</b> possessed excellent antimalarial activity (EC<sub>50</sub> = 5.9/3.7 nM), which was better than that of artesunic acid (EC<sub>50</sub> = 8.2 nM) and chloroquine (EC<sub>50</sub> = 9.8 nM). Overall, most of the presented thymoquinone-artemisinin-based hybrids exhibit an excellent and broad variety of biological activities (anticancer, antimalarial, and antiviral) combined with a low toxicity/high selectivity profile.
- Addresses
- Organic Chemistry Chair I and Interdisciplinary Center for Molecular Materials (ICMM), Friedrich-Alexander University of Erlangen-Nürnberg, Nikolaus-Fiebiger-Straße 10, 91058 Erlangen, Germany.
- Autoren
- Tony Fröhlich
- Christoph Reiter
- Mohamed EM Saeed
- Corina Hutterer
- Friedrich Hahn
- Maria Leidenberger
- Oliver Friedrich
- Barbara Kappes
- Manfred Marschall
- Thomas Efferth
- Svetlana B Tsogoeva
- DOI
- 10.1021/acsmedchemlett.7b00412
- eISSN
- 1948-5875
- Externe Identifier
- PubMed Identifier: 29937978
- PubMed Central ID: PMC6004568
- Funding acknowledgements
- Deutsche Forschungsgemeinschaft: 1289/7-1/7-3
- Friedrich-Alexander-Universit?t Erlangen-N?rnberg:
- Deutsche Forschungsgemeinschaft: 87/16-3
- Open access
- false
- ISSN
- 1948-5875
- Ausgabe der Veröffentlichung
- 6
- Zeitschrift
- ACS medicinal chemistry letters
- Sprache
- eng
- Medium
- Electronic-eCollection
- Online publication date
- 2017
- Paginierung
- 534 - 539
- Datum der Veröffentlichung
- 2018
- Status
- Published
- Datum der Datenerfassung
- 2018
- Titel
- Synthesis of Thymoquinone-Artemisinin Hybrids: New Potent Antileukemia, Antiviral, and Antimalarial Agents.
- Sub types
- rapid-communication
- Journal Article
- Ausgabe der Zeitschrift
- 9
Files
https://europepmc.org/articles/PMC6004568?pdf=render
Data source: Europe PubMed Central
- Abstract
- A series of hybrid compounds based on the natural products artemisinin and thymoquinone was synthesized and investigated for their biological activity against the malaria parasite Plasmodium falciparum 3D7 strain, human cytomegalovirus (HCMV), and two leukemia cell lines (drug-sensitive CCRF-CEM and multidrug-resistant subline CEM/ADR5000). An unprecedented one-pot method of selective formation of C-10α-acetate 14 starting from a 1:1 mixture of C-10α- to C-10β-dihydroartemisinin was developed. The key step of this facile method is a mild decarboxylative activation of malonic acid mediated by DCC/DMAP. Ether-linked thymoquinone-artemisinin hybrids 6a/b stood out as the most active compounds in all categories, while showing no toxic side effects toward healthy human foreskin fibroblasts and thus being selective. They exhibited EC50 values of 0.2 μM against the doxorubicin-sensitive as well as the multidrug-resistant leukemia cells and therefore can be regarded as superior to doxorubicin. Moreover, they showed to be five times more active than the standard drug ganciclovir and nearly eight times more active than artesunic acid against HCMV. In addition, hybrids 6a/b possessed excellent antimalarial activity (EC50 = 5.9/3.7 nM), which was better than that of artesunic acid (EC50 = 8.2 nM) and chloroquine (EC50 = 9.8 nM). Overall, most of the presented thymoquinone-artemisinin-based hybrids exhibit an excellent and broad variety of biological activities (anticancer, antimalarial, and antiviral) combined with a low toxicity/high selectivity profile.
- Date of acceptance
- 2017
- Autoren
- Tony Fröhlich
- Christoph Reiter
- Mohamed EM Saeed
- Corina Hutterer
- Friedrich Hahn
- Maria Leidenberger
- Oliver Friedrich
- Barbara Kappes
- Manfred Marschall
- Thomas Efferth
- Svetlana B Tsogoeva
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/29937978
- DOI
- 10.1021/acsmedchemlett.7b00412
- Externe Identifier
- PubMed Central ID: PMC6004568
- ISSN
- 1948-5875
- Ausgabe der Veröffentlichung
- 6
- Zeitschrift
- ACS Med Chem Lett
- Sprache
- eng
- Country
- United States
- Paginierung
- 534 - 539
- Datum der Veröffentlichung
- 2018
- Status
- Published online
- Titel
- Synthesis of Thymoquinone-Artemisinin Hybrids: New Potent Antileukemia, Antiviral, and Antimalarial Agents.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 9
Data source: PubMed
- Beziehungen:
- Property of