Synthesis of halogenated 4-quinolones and evaluation of their antiplasmodial activity.

Treatment of 4-hydroxyquinolines with (2-methyl)allyl bromide in the presence of K2CO3 resulted in the formation of novel N-[(2-methyl)allyl]-4-quinolones through selective N-alkylation. Further reaction of N-(2-methylallyl)-4-quinolones with bromine or N-bromosuccinimide yielded the corresponding 3-bromo-1-(2,3-dibromo-2-methylpropyl)-4-quinolones and 3-bromo-1-(2-methylallyl)-4-quinolones, respectively. Furthermore, a copper-catalyzed C-N coupling of the latter 3-bromo-4-quinolones with (5-chloro)indole afforded novel 3-[(5-chloro)indol-1-yl]-4-quinolone hybrids. Antifungal and antiplasmodial assays of all new 4-quinolones were performed and revealed no antifungal properties but moderate antiplasmodial activities. All 15 compounds displayed micromolar activities against a chloroquine-sensitive strain of Plasmodium falciparum, and the five most potent compounds also showed micromolar activities against a chloroquine-resistant strain of P. falciparum with IC50-values ranging between 4 and 70 µM.

Evaluation of (4-aminobutyloxy)quinolines as a novel class of antifungal agents.

Antifungal assessment of eighteen 5-, 6- and 8-(4-aminobutyloxy)quinolines revealed a significant susceptibility of the tested fungi and yeast strains (Candida albicans, Rhodotorula bogoriensis, Aspergillus flavus and Fusarium solani) toward different halo-substituted 8-(4-aminobutyloxy)quinolines. The six most potent compounds displayed antifungal activities similar to those of established antifungal agents such as Amphotericin B, Fluconazole and Itraconazole, and one representative also showed a promising broad-spectrum antifungal profile. The introduction of an aminoalkoxy side chain at the 8-position of a halo-substituted quinoline core might thus provide a new class of lead structures in the search for novel antifungal agents.

Biocatalytic production of novel glycolipids with cellodextrin phosphorylase.

Glycolipids have gained increasing attention as natural surfactants with a beneficial environmental profile. They are typically produced by fermentation, which only gives access to a limited number of structures. Here we describe the biocatalytic production of novel glycolipids with the cellodextrin phosphorylase from Clostridium stercorarium. This enzyme was found to display a broad donor and acceptor specificity, allowing the synthesis of five different products. Indeed, using either α-glucose 1-phosphate or α-galactose 1-phosphate as glycosyl donor, sophorolipid as well as glucolipid could be efficiently glycosylated. The transfer of a glucosyl moiety afforded a mixture of products that precipitated from the solution, resulting in near quantitative yields. The transfer of a galactosyl moiety, in contrast, generated a single product that remained in solution at thermodynamic equilibrium. These glycolipids not only serve as a new class of biosurfactants, but could also have applications in the pharmaceutical and nanomaterials industries.