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

Reiter C, Fröhlich T, Gruber L, Hutterer C, Marschall M, Voigtländer C, Friedrich O, Kappes B, Efferth T, Tsogoeva S (2015)

Publication Language: English

Publication Status: Published

Publication Type: Journal article, Original article

Publication year: 2015

Journal

Bioorganic & Medicinal Chemistry Elsevier

Publisher: Elsevier

URI: http://www.sciencedirect.com/science/article/pii/S096808961500632X

DOI: 10.1016/j.bmc.2015.07.048

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).

Authors with CRIS profile

Christoph Reiter Professur für Organische Chemie Tony Fröhlich Lehrstuhl für Organische Chemie I Manfred Marschall Lehrstuhl für Klinische und Molekulare Virologie Cornelia Voigtländer Lehrstuhl für Medizinische Biotechnologie Oliver Friedrich Lehrstuhl für Medizinische Biotechnologie Bärbel Kappes Lehrstuhl für Medizinische Biotechnologie Svetlana Tsogoeva Professur für Organische Chemie

Involved external institutions

Johannes Gutenberg-Universität Mainz (JGU) DE Germany (DE)

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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