Synthesis of Artemisinin-Derived Dimers, Trimers and Dendrimers: Investigation of Their Antimalarial and Antiviral Activities Including Putative Mechanisms of Action

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autorinnen und Autoren: Fröhlich T, Hahn F, Belmudes L, Leidenberger M, Friedrich O, Kappes B, Coute Y, Marschall M, Tsogoeva S
Zeitschrift: Chemistry - A European Journal
Jahr der Veröffentlichung: 2018
Band: 24
Heftnummer: 32
Seitenbereich: 8103-8113
ISSN: 0947-6539
eISSN: 1521-3765


Abstract

Generation of dimers, trimers and dendrimers of bioactive compounds is an approach that has recently been developed for the discovery of new potent drug candidates. Herein, we present the synthesis of new artemisinin-derived dimers and dendrimers and investigate their action against malaria parasite Plasmodium falciparum 3D7 strain and human cytomegalovirus (HCMV). Dimer 7 was the most active compound (EC50 1.4 nm) in terms of antimalarial efficacy and was even more effective than the standard drugs dihydroartemisinin (EC50 2.4 nm), artesunic acid (EC50 8.9 nm) and chloroquine (EC50 9.8 nm). Trimer 4 stood out as the most active agent against HCMV in vitro replication and exerted an EC50 value of 0.026 mu m, representing an even higher activity than the two reference drugs ganciclovir (EC50 2.60 mu m) and artesunic acid (EC50 5.41 mu m). In addition, artemisinin-derived dimer 13 and trimer 15 were for the first time both immobilized on TOYOPEARL AF-Amino-650M beads and used for mass spectrometry-based target identification experiments using total lysates of HCMV-infected primary human fibroblasts. Two major groups of novel target candidates, namely cytoskeletal and mitochondrial proteins were obtained. Two putatively compound-binding viral proteins, namely major capsid protein (MCP) and envelope glycoprotein pUL132, which are both essential for HCMV replication, were identified.


FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Friedrich, Oliver Prof. Dr. Dr.
Lehrstuhl für Medizinische Biotechnologie
Fröhlich, Tony
Lehrstuhl für Organische Chemie I
Hahn, Friedrich
Professur für Virologie
Kappes, Bärbel Prof. Dr.
Lehrstuhl für Medizinische Biotechnologie
Leidenberger, Maria
Lehrstuhl für Medizinische Biotechnologie
Marschall, Manfred apl. Prof. Dr.
Medizinische Fakultät
Tsogoeva, Svetlana Prof. Dr.
Professur für Organische Chemie


Einrichtungen weiterer Autorinnen und Autoren

University of Grenoble Alpes (UGA) / Université de Grenoble


Zitierweisen

APA:
Fröhlich, T., Hahn, F., Belmudes, L., Leidenberger, M., Friedrich, O., Kappes, B.,... Tsogoeva, S. (2018). Synthesis of Artemisinin-Derived Dimers, Trimers and Dendrimers: Investigation of Their Antimalarial and Antiviral Activities Including Putative Mechanisms of Action. Chemistry - A European Journal, 24(32), 8103-8113. https://dx.doi.org/10.1002/chem.201800729

MLA:
Fröhlich, Tony, et al. "Synthesis of Artemisinin-Derived Dimers, Trimers and Dendrimers: Investigation of Their Antimalarial and Antiviral Activities Including Putative Mechanisms of Action." Chemistry - A European Journal 24.32 (2018): 8103-8113.

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Zuletzt aktualisiert 2019-31-01 um 16:10