The broad-spectrum antiinfective drug artesunate interferes with the canonical nuclear factor kappa B (NF-κB) pathway by targeting RelA/p65

Beitrag in einer Fachzeitschrift
(Originalarbeit)


Details zur Publikation

Autorinnen und Autoren: Hutterer C, Niemann I, Milbradt J, Fröhlich T, Reiter C, Kadioglu O, Bahsi H, Zeitträger I, Wagner S, Einsiedel J, Gmeiner P, Vogel N, Wandinger S, Godl K, Stamminger T, Efferth T, Tsogoeva S, Marschall M
Zeitschrift: Antiviral Research
Jahr der Veröffentlichung: 2015
Band: 124
Seitenbereich: 101-109
ISSN: 1872-9096
Sprache: Englisch


Abstract


Infection with human cytomegalovirus (HCMV) is a serious medical problem, particularly in immunocompromised individuals and neonates. The success of standard antiviral therapy is hampered by low drug compatibility and induction of viral resistance. A novel strategy is based on the exploitation of cell-directed signaling inhibitors. The broad antiinfective drug artesunate (ART) offers additional therapeutic options such as oral bioavailability and low levels of toxic side-effects. Here, novel ART-derived compounds including dimers and trimers were synthesized showing further improvements over the parental drug. Antiviral activity and mechanistic aspects were determined leading to the following statements: (i) ART exerts antiviral activity towards human and animal herpesviruses, (ii) no induction of ART-resistant HCMV mutants occurred in vitro, (iii) chemically modified derivatives of ART showed strongly enhanced anti-HCMV efficacy, (iv) NF-κB reporter constructs, upregulated during HCMV replication, could be partially blocked by ART treatment, (v) ART activity analyzed in stable reporter cell clones indicated an inhibition of stimulated NF-κB but not CREB pathway, (vi) solid-phase immobilized ART was able to bind to NF-κB RelA/p65, and (vii) peptides within NF-κB RelA/p65 represent candidates of ART binding as analyzed by in silico docking and mass spectrometry. These novel findings open new prospects for the future medical use of ART and ART-related drug candidates.



FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Einsiedel, Jürgen Dr.
Lehrstuhl für Pharmazeutische Chemie
Fröhlich, Tony
Lehrstuhl für Organische Chemie I
Gmeiner, Peter Prof. Dr.
Lehrstuhl für Pharmazeutische Chemie
Milbradt, Jens PD Dr.
Sonderforschungsbereich 796 (mit integriertem Graduiertenkolleg) Steuerungsmechanismen mikrobieller Effektoren in Wirtszellen
Niemann, Ina
Professur für Virologie
Reiter, Christoph
Lehrstuhl für Organische Chemie I
Stamminger, Thomas Prof. Dr.
Professur für Virologie
Tsogoeva, Svetlana Prof. Dr.
Professur für Organische Chemie
Vogel, Nicolas Dr.
Lehrstuhl für Biochemie und Molekulare Medizin


Zusätzliche Organisationseinheit(en)
Emil-Fischer-Zentrum (Emil Fischer Center)


Einrichtungen weiterer Autorinnen und Autoren

Evotec AG
Johannes Gutenberg-Universität Mainz


Zitierweisen

APA:
Hutterer, C., Niemann, I., Milbradt, J., Fröhlich, T., Reiter, C., Kadioglu, O.,... Marschall, M. (2015). The broad-spectrum antiinfective drug artesunate interferes with the canonical nuclear factor kappa B (NF-κB) pathway by targeting RelA/p65. Antiviral Research, 124, 101-109. https://dx.doi.org/10.1016/j.antiviral.2015.10.003

MLA:
Hutterer, Corina, et al. "The broad-spectrum antiinfective drug artesunate interferes with the canonical nuclear factor kappa B (NF-κB) pathway by targeting RelA/p65." Antiviral Research 124 (2015): 101-109.

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Zuletzt aktualisiert 2019-18-07 um 07:22