Highly potent artemisinin-derived dimers and trimers: Synthesis and evaluation of their antimalarial, antileukemia and antiviral activities.

Journal article
(Original article)


Publication Details

Author(s): Reiter C, Fröhlich T, Gruber L, Hutterer C, Marschall M, Voigtländer C, Friedrich O, Kappes B, Efferth T, Tsogoeva S
Journal: Bioorganic & medicinal chemistry
Publisher: Elsevier
Publication year: 2015
ISSN: 1464-3391
Language: English


Abstract


New pharmaceutically active compounds can be obtained by modification of existing drugs to access more effective agents in the wake of drug resistance amongst others. To achieve this goal the concept of hybridization was established during the last decade. We employed this concept by coupling two artemisinin-derived precursors to obtain dimers or trimers with increased in vitro activity against Plasmodiumfalciparum 3D7 strain, leukemia cells (CCRF-CEM and multidrug-resistant subline CEM/ADR5000) and human cytomegalovirus (HCMV). Dimer 4 (IC50 of 2.6nM) possess superior antimalarial activity compared with its parent compound artesunic acid(3) (IC50 of 9.0nM). Dimer5 and trimers6 and 7 display superior potency against both leukemia cell lines (IC50 up to 0.002μM for CCRF-CEM and IC50 up to 0.20μM for CEM/ADR5000) and are even more active than clinically used doxorubicin (IC50 1.61μM for CEM/ADR5000). With respect to anti-HCMV activity, trimer6 is the most efficient hybrid (IC50 0.04μM) outperforming ganciclovir (IC50 2.6μM), dihydroartemisinin(IC50 >10μM) and artesunic acid (IC50 3.8μM).



FAU Authors / FAU Editors

Friedrich, Oliver Prof. Dr. Dr.
Lehrstuhl für Medizinische Biotechnologie
Fröhlich, Tony
Lehrstuhl für Organische Chemie I
Kappes, Bärbel Prof. Dr.
Lehrstuhl für Medizinische Biotechnologie
Reiter, Christoph
Professur für Organische Chemie
Tsogoeva, Svetlana Prof. Dr.
Professur für Organische Chemie
Voigtländer, Cornelia
Lehrstuhl für Medizinische Biotechnologie


External institutions with authors

Johannes Gutenberg-Universität Mainz


How to cite

APA:
Reiter, C., Fröhlich, T., Gruber, L., Hutterer, C., Marschall, M., Voigtländer, C.,... Tsogoeva, S. (2015). Highly potent artemisinin-derived dimers and trimers: Synthesis and evaluation of their antimalarial, antileukemia and antiviral activities. Bioorganic & medicinal chemistry. https://dx.doi.org/10.1016/j.bmc.2015.07.048

MLA:
Reiter, Christoph, et al. "Highly potent artemisinin-derived dimers and trimers: Synthesis and evaluation of their antimalarial, antileukemia and antiviral activities." Bioorganic & medicinal chemistry (2015).

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Last updated on 2019-21-07 at 07:20