title: New efficient artemisinin derived agents against human leukemia cells, human cytomegalovirus and Plasmodium falciparum: 2nd generation 1,2,4-trioxane-ferrocene hybrids.
abstract: In our ongoing search for highly active hybrid molecules exceeding their parent compounds in anticancer, antimalaria as well as antiviral activity and being an alternative to the standard drugs, we present the synthesis and biological investigations of 2nd generation 1,2,4-trioxane-ferrocene hybrids. In vitro tests against the CCRF-CEM leukemia cell line revealed di-1,2,4-trioxane-ferrocene hybrid 7 as the most active compound (IC50 of 0.01 μM). Regarding the activity against the multidrug resistant subline CEM/ADR5000, 1,2,4-trioxane-ferrocene hybrid 5 showed a remarkable activity (IC50 of 0.53 μM). Contrary to the antimalaria activity of hybrids 4-8 against Plasmodium falciparum 3D7 strain with slightly higher IC50 values (between 7.2 and 30.2 nM) than that of their parent compound DHA, hybrids 5-7 possessed very promising activity (IC50 values lower than 0.5 μM) against human cytomegalovirus (HCMV). The application of 1,2,4-trioxane-ferrocene hybrids against HCMV is unprecedented and demonstrated here for the first time.
authors.affiliation: Department of Chemistry and Pharmacy, Organic Chemistry Chair I and Interdisciplinary Center for Molecular Materials (ICMM), University of Erlangen-Nuremberg, Henkestraße 42, 91054 Erlangen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Reiter
authors.affiliation: Department of Chemistry and Pharmacy, Organic Chemistry Chair I and Interdisciplinary Center for Molecular Materials (ICMM), University of Erlangen-Nuremberg, Henkestraße 42, 91054 Erlangen, Germany.
authors.forename: Tony
authors.initials: T
authors.lastname: Fröhlich
authors.affiliation: Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Staudinger Weg 5, 55128 Mainz, Germany.
authors.forename: Maen
authors.initials: M
authors.lastname: Zeino
authors.affiliation: Institute for Clinical and Molecular Virology, University of Erlangen-Nuremberg, Schloßgarten 4, 91054 Erlangen, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Marschall
authors.affiliation: Institute for Clinical and Molecular Virology, University of Erlangen-Nuremberg, Schloßgarten 4, 91054 Erlangen, Germany.
authors.forename: Hanife
authors.initials: H
authors.lastname: Bahsi
authors.affiliation: Institute of Medical Biotechnology, University of Erlangen-Nuremberg, Paul-Gordan-Straße 3, 91052 Erlangen, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Leidenberger
authors.affiliation: Institute of Medical Biotechnology, University of Erlangen-Nuremberg, Paul-Gordan-Straße 3, 91052 Erlangen, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Friedrich
authors.affiliation: Institute of Medical Biotechnology, University of Erlangen-Nuremberg, Paul-Gordan-Straße 3, 91052 Erlangen, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Kappes
authors.affiliation: Department of Chemistry and Pharmacy, Organic Chemistry Chair I and Interdisciplinary Center for Molecular Materials (ICMM), University of Erlangen-Nuremberg, Henkestraße 42, 91054 Erlangen, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Hampel
authors.affiliation: Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Staudinger Weg 5, 55128 Mainz, Germany. Electronic address: efferth@uni-mainz.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Efferth
authors.affiliation: Department of Chemistry and Pharmacy, Organic Chemistry Chair I and Interdisciplinary Center for Molecular Materials (ICMM), University of Erlangen-Nuremberg, Henkestraße 42, 91054 Erlangen, Germany. Electronic address: svetlana.tsogoeva@fau.de.
authors.forename: Svetlana B
authors.initials: SB
authors.lastname: Tsogoeva
mesh_terms: D037621:Artemisinins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple / Q000187:drug effects; D005296:Ferrous Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D007938:Leukemia / Q000188:drug therapy; D000075163:Metallocenes; D010963:Plasmodium falciparum / Q000187:drug effects*
chemical_list: C503429:1,2,4-trioxane; D037621:Artemisinins; D005296:Ferrous Compounds; D006571:Heterocyclic Compounds; D006576:Heterocyclic Compounds, 4 or More Rings; D000075163:Metallocenes; C031327:artemisinin; C004998:ferrocene
keywords: Artemisinin; Cancer; Ferrocene; Human cytomegalovirus; Hybrid; Malaria