Synthesis of Artemisinin-Estrogen Hybrids Highly Active against HCMV, P-falciparum, and Cervical and Breast Cancer

Journal article


Publication Details

Author(s): Fröhlich T, Kiss A, Wolfling J, Mernyak E, Kulmany AE, Minorics R, Zupko I, Leidenberger M, Friedrich O, Kappes B, Hahn F, Marschall M, Schneider G, Tsogoeva S
Journal: Acs Medicinal Chemistry Letters
Publication year: 2018
Volume: 9
Journal issue: 11
Pages range: 1128-1133
ISSN: 1948-5875


Abstract

Artemisinin-estrogen hybrids were for the first time both synthesized and investigated for their in vitro biological activity against malaria parasites (Plasmodium falciparum 3D7), human cytomegalovirus (HCMV), and a panel of human malignant cells of gynecological origin containing breast (MCF7, MDA-MB-231, MDA-MB-361, T47D) and cervical tumor cell lines (HeLa, SiHa, C33A). In terms of antimalarial efficacy, hybrid 8 (EC50 = 3.8 nM) was about two times more active than its parent compound artesunic acid (7) (EC50 = 8.9 nM) as well as the standard drug chloroquine (EC50 = 9.8 nM) and was, therefore, comparable to the clinically used dihydroartemisinin (6) (EC50 = 2.4 nM). Furthermore, hybrids 9-12 showed a strong antiviral effect with EC50 values in the submicromolar range (0.22-0.38 mu M) and thus possess profoundly stronger anti-HCMV activity (approximately factor 25) than the parent compound artesunic acid (7) (EC50 = 5.41 mu M). These compounds also exerted a higher in vitro anti-HCMV efficacy than ganciclovir used as the standard of current antiviral treatment. In addition, hybrids 8-12 elicited substantially more pronounced growth inhibiting action on all cancer cell lines than their parent compounds and the reference drug cisplatin. The most potent agent, hybrid 12, exhibited submicromolar EC50 values (0.15-0.93 mu M) against breast cancer and C33A cell lines.


FAU Authors / FAU Editors

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


External institutions with authors

University of Szeged / József Attila Tudományegyetem Szeged


How to cite

APA:
Fröhlich, T., Kiss, A., Wolfling, J., Mernyak, E., Kulmany, A.E., Minorics, R.,... Tsogoeva, S. (2018). Synthesis of Artemisinin-Estrogen Hybrids Highly Active against HCMV, P-falciparum, and Cervical and Breast Cancer. Acs Medicinal Chemistry Letters, 9(11), 1128-1133. https://dx.doi.org/10.1021/acsmedchemlett.8b00381

MLA:
Fröhlich, Tony, et al. "Synthesis of Artemisinin-Estrogen Hybrids Highly Active against HCMV, P-falciparum, and Cervical and Breast Cancer." Acs Medicinal Chemistry Letters 9.11 (2018): 1128-1133.

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Last updated on 2019-31-01 at 18:10