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

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 (2018)

Publication Type: Journal article

Publication year: 2018

Journal

ACS Medicinal Chemistry Letters American Chemical Society

Book Volume: 9

Pages Range: 1128-1133

Journal Issue: 11

DOI: 10.1021/acsmedchemlett.8b00381

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.

Authors with CRIS profile

Tony Fröhlich Professur für Organische Chemie Maria Leidenberger Lehrstuhl für Medizinische Biotechnologie Oliver Friedrich Lehrstuhl für Medizinische Biotechnologie Bärbel Kappes Lehrstuhl für Medizinische Biotechnologie Friedrich Hahn Professur für Virologie Manfred Marschall Lehrstuhl für Klinische und Molekulare Virologie Svetlana Tsogoeva Professur für Organische Chemie

Involved external institutions

University of Szeged / József Attila Tudományegyetem Szeged HU Hungary (HU)

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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