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

Tony Fröhlich, Anita Kiss, J. Wölfling, E. Mernyák, Ágnes E. Kulmány, Renáta Minorics, I. Zupkó, Maria Leidenberger, Oliver Friedrich, Barbara Kappes, Friedrich Hahn, Manfred Marschall, G. Schneider, Svetlana B. Tsogoeva

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 μM) and thus possess profoundly stronger anti-HCMV activity (approximately factor 25) than the parent compound artesunic acid (7) (EC50 = 5.41 μM). 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 μM) against breast cancer and C33A cell lines.

Original languageEnglish
Pages (from-to)1128-1133
Number of pages6
JournalACS Medicinal Chemistry Letters
Volume9
Issue number11
DOIs
Publication statusPublished - Nov 8 2018

Fingerprint

Cytomegalovirus
Uterine Cervical Neoplasms
Estrogens
dihydroartemisinin
Cells
Breast Neoplasms
Antiviral Agents
Ganciclovir
Chloroquine
Antimalarials
Bioactivity
Pharmaceutical Preparations
Cisplatin
Tumors
Cell Line
Falciparum Malaria
Tumor Cell Line
Human Activities
Parasites
Breast

Keywords

  • anticancer activity
  • antimalarial activity
  • antiviral activity
  • Artemisinin
  • estrogen

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

Cite this

Synthesis of Artemisinin-Estrogen Hybrids Highly Active against HCMV, P. falciparum, and Cervical and Breast Cancer. / Fröhlich, Tony; Kiss, Anita; Wölfling, J.; Mernyák, E.; Kulmány, Ágnes E.; Minorics, Renáta; Zupkó, I.; Leidenberger, Maria; Friedrich, Oliver; Kappes, Barbara; Hahn, Friedrich; Marschall, Manfred; Schneider, G.; Tsogoeva, Svetlana B.

In: ACS Medicinal Chemistry Letters, Vol. 9, No. 11, 08.11.2018, p. 1128-1133.

Research output: Contribution to journalArticle

Fröhlich, T, Kiss, A, Wölfling, J, Mernyák, E, Kulmány, ÁE, Minorics, R, Zupkó, I, Leidenberger, M, Friedrich, O, Kappes, B, Hahn, F, Marschall, M, Schneider, G & Tsogoeva, SB 2018, 'Synthesis of Artemisinin-Estrogen Hybrids Highly Active against HCMV, P. falciparum, and Cervical and Breast Cancer', ACS Medicinal Chemistry Letters, vol. 9, no. 11, pp. 1128-1133. https://doi.org/10.1021/acsmedchemlett.8b00381
Fröhlich, Tony ; Kiss, Anita ; Wölfling, J. ; Mernyák, E. ; Kulmány, Ágnes E. ; Minorics, Renáta ; Zupkó, I. ; Leidenberger, Maria ; Friedrich, Oliver ; Kappes, Barbara ; Hahn, Friedrich ; Marschall, Manfred ; Schneider, G. ; Tsogoeva, Svetlana B. / Synthesis of Artemisinin-Estrogen Hybrids Highly Active against HCMV, P. falciparum, and Cervical and Breast Cancer. In: ACS Medicinal Chemistry Letters. 2018 ; Vol. 9, No. 11. pp. 1128-1133.
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AU - Friedrich, Oliver

AU - Kappes, Barbara

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AU - Tsogoeva, Svetlana B.

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