RESUMO
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.
Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Antiprotozoários/síntese química , Antiprotozoários/farmacologia , Paládio/química , Quinonas/síntese química , Quinonas/farmacologia , Antibacterianos/química , Antiprotozoários/química , Catálise , Técnicas de Química Sintética , Mycobacterium smegmatis/efeitos dos fármacos , Plasmodium falciparum/efeitos dos fármacos , Quinonas/química , Trypanosoma brucei rhodesiense/efeitos dos fármacosRESUMO
Little is known about the pharmacological activities of Iris adriatica (Iridaceae), a plant endemic to Dalmatia (Croatia). We therefore performed a bioassay-guided fractionation including high-performance counter current chromatography (HPCCC) and antibacterial tests using Mycobacterium smegmatis mc2 155. One obtained fraction was found to be antimycobacterially active with a MIC of 64 mg L-1. Furthermore, fractions were tested for resistance modulatory effects using ethidium bromide as substrate. We were able to identify the pure isoflavonic compounds irigenin and irilone and a fraction containing mainly benzophenone 2,4,6-trihydroxy-4-methoxy-benzophenone, responsible for the resistance-modulatory activity of this plant.