2. Academic Validation
  3. Access to new highly potent antileukemia, antiviral and antimalarial agents via hybridization of natural products (homo)egonol, thymoquinone and artemisinin

Access to new highly potent antileukemia, antiviral and antimalarial agents via hybridization of natural products (homo)egonol, thymoquinone and artemisinin

  • Bioorg Med Chem. 2018 Jul 23;26(12):3610-3618. doi: 10.1016/j.bmc.2018.05.041.
Aysun Çapcı Karagöz 1,  Christoph Reiter 1,  Ean-Jeong Seo 2,  Lisa Gruber 2,  Friedrich Hahn 3,  Maria Leidenberger 4,  Volker Klein 1,  Frank Hampel 1,  Oliver Friedrich 4,  Manfred Marschall 3,  Barbara Kappes 4,  Thomas Efferth 2,  Svetlana B Tsogoeva 5
Affiliations

Affiliations

  • 1 Organic Chemistry Chair I and Interdisciplinary Center for Molecular Materials (ICMM), Friedrich-Alexander University of Erlangen-Nürnberg, Nikolaus-Fiebiger-Straße 10, 91058 Erlangen, Germany.
  • 2 Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Staudinger Weg 5, 55128 Mainz, Germany.
  • 3 Institute for Clinical and Molecular Virology, Friedrich-Alexander University of Erlangen-Nürnberg, Schlossgarten 4, 91054 Erlangen, Germany.
  • 4 Institute of Medical Biotechnology, Friedrich-Alexander University of Erlangen-Nürnberg, Paul-Gordon-Straße 3, 91052 Erlangen, Germany.
  • 5 Organic Chemistry Chair I and Interdisciplinary Center for Molecular Materials (ICMM), Friedrich-Alexander University of Erlangen-Nürnberg, Nikolaus-Fiebiger-Straße 10, 91058 Erlangen, Germany. Electronic address: svetlana.tsogoeva@fau.de.
PMID: 29887512 DOI: 10.1016/j.bmc.2018.05.041
Abstract

Hybridization of Natural Products has high potential to further improve their activities and may produce synergistic effects between linked pharmacophores. Here we report synthesis of nine new hybrids of Natural Products egonol, homoegonol, thymoquinone and artemisinin and evaluation of their activities against P. falciparum 3D7 parasites, human cytomegalovirus, sensitive and multidrug-resistant human leukemia cells. Most of the new hybrids exceed their parent compounds in antimalarial, Antiviral and antileukemia activities and in some cases show higher in vitro efficacy than clinically used reference drugs chloroquine, ganciclovir and doxorubicin. Combined, our findings stress the high potency of these hybrids and encourages further use of the hybridization concept in applied pharmacological research.

Keywords

Antileukemia activity; Antimalarial activity; Antiviral activity; Artemisinin; Egonol; Natural product hybrid; Thymoquinone.

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