Synthesis of Novel Hybrids of Quinazoline and Artemisinin with High Activities against Plasmodium falciparum, Human Cytomegalovirus, and Leukemia Cells

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Details zur Publikation

Autor(en): Fröhlich T, Reiter C, Ibrahim MM, Beutel J, Hutterer C, Zeitträger I, Bahsi H, Leidenberger M, Friedrich O, Kappes B, Efferth T, Marschall M, Tsogoeva S
Zeitschrift: ACS Omega
Jahr der Veröffentlichung: 2017
Band: 2
Heftnummer: 6
Seitenbereich: 2422-2431
ISSN: 2470-1343


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.


FAU-Autoren / FAU-Herausgeber

Beutel, Jannis
Lehrstuhl für Pharmazeutische Chemie
Friedrich, Oliver Prof. Dr. Dr.
Lehrstuhl für Medizinische Biotechnologie
Fröhlich, Tony
Lehrstuhl für Organische Chemie I
Kappes, Bärbel Prof. Dr.
Lehrstuhl für Medizinische Biotechnologie
Leidenberger, Maria
Lehrstuhl für Medizinische Biotechnologie
Tsogoeva, Svetlana Prof. Dr.
Professur für Organische Chemie


Autor(en) der externen Einrichtung(en)
Johannes Gutenberg-Universität Mainz


Zitierweisen

APA:
Fröhlich, T., Reiter, C., Ibrahim, M.M., Beutel, J., Hutterer, C., Zeitträger, I.,... Tsogoeva, S. (2017). Synthesis of Novel Hybrids of Quinazoline and Artemisinin with High Activities against Plasmodium falciparum, Human Cytomegalovirus, and Leukemia Cells. ACS Omega, 2(6), 2422-2431. https://dx.doi.org/10.1021/acsomega.7b00310

MLA:
Fröhlich, Tony, et al. "Synthesis of Novel Hybrids of Quinazoline and Artemisinin with High Activities against Plasmodium falciparum, Human Cytomegalovirus, and Leukemia Cells." ACS Omega 2.6 (2017): 2422-2431.

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Zuletzt aktualisiert 2019-07-06 um 09:48