Palladium-catalysed synthesis of arylnaphthoquinones as antiprotozoal and antimycobacterial agents.
Eur J Med Chem
; 207: 112837, 2020 Dec 01.
Article
in En
| MEDLINE
| ID: mdl-33002847
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.) mc2 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Palladium
/
Quinones
/
Anti-Bacterial Agents
/
Antiprotozoal Agents
Language:
En
Journal:
Eur J Med Chem
Year:
2020
Document type:
Article
Affiliation country: