Palladium-catalysed synthesis of arylnaphthoquinones as antiprotozoal and antimycobacterial agents

Marc-Manuel Kalt, Wolfgang Schuehly, Robert Saf, Sandra Ochensberger, Julia Solnier, Franz Bucar, Marcel Kaiser, Armin Presser*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Malaria and tuberculosis are still among the leading causes of death in low-income countries. The 1,4-naphthoquinone (NQ) scaffold can be found in a variety of anti-infective agents. Herein, we report an optimised, high yield process for the preparation of various 2-arylnaphthoquinones by a palladium-catalysed Suzuki reaction. All synthesised compounds were evaluated for their in-vitro antiprotozoal and antimycobacterial activity. Antiprotozoal activity was assessed against Plasmodium falciparum (P.f.) NF54 and Trypanosoma brucei rhodesiense (T.b.r.) STIB900, and antimycobacterial activity against Mycobacterium smegmatis (M.s.) mc 2 155. Substitution with pyridine and pyrimidine rings significantly increased antiplasmodial potency of our compounds. The 2-aryl-NQs exhibited trypanocidal activity in the nM range with a very favourable selectivity profile. (Pseudo)halogenated aryl-NQs were found to have a pronounced effect indicating inhibition of mycobacterial efflux pumps. Cytotoxicity of all compounds towards L6 cells was evaluated and the respective selectivity indices (SI) were calculated. In addition, the physicochemical parameters of the synthesised compounds were discussed.

Original languageEnglish
Article number112837
JournalEuropean Journal of Medicinal Chemistry
Publication statusPublished - 1 Dec 2020


  • Antiprotozoal
  • Tuberculosis
  • Suzuki cross-coupling
  • Naphthoquinone

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Organic Chemistry


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