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

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Details zur Publikation

Autor(en): 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
Zeitschrift: Acs Medicinal Chemistry Letters
Jahr der Veröffentlichung: 2018
Band: 9
Heftnummer: 11
Seitenbereich: 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-Autoren / FAU-Herausgeber

Friedrich, Oliver Prof. Dr. Dr.
Lehrstuhl für Medizinische Biotechnologie
Fröhlich, Tony
Professur für Organische Chemie
Hahn, Friedrich
Professur für Virologie
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)
University of Szeged / József Attila Tudományegyetem Szeged


Zitierweisen

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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Zuletzt aktualisiert 2019-31-01 um 18:10