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Palladium-catalysed synthesis of arylnaphthoquinones as antiprotozoal and antimycobacterial agents

Kalt, M. M. and Schuehly, W. and Saf, R. and Ochensberger, S. and Solnier, J. and Bucar, F. and Kaiser, M. and Presser, A.. (2020) Palladium-catalysed synthesis of arylnaphthoquinones as antiprotozoal and antimycobacterial agents. Eur J Med Chem, 207. p. 112837.

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Abstract

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.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Parasite Chemotherapy (Mäser)
UniBasel Contributors:Kaiser, Marcel
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:1768-3254 (Electronic)0223-5234 (Linking)
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:28 Dec 2022 13:17
Deposited On:28 Dec 2022 13:17

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