Synthesis of xanthone-1,2,3-triazole dyads

Xanthones and 1,2,3-triazoles are known to exhibit several biological, pharmacological and biocidal properties[1]. The potential applications of these two classes of heterocycles led us to develop new strategies to synthesize xanthone-1,2,3-triazole dyads, aiming to get potentially improved therapeutic agents[2]. With this rational in mind we designed and synthesized novel chromone derivatives 1a-d to be used as building motifs and to explore the reactivity of the two unsaturated systems (the diene and the alkyne). In the present communication we will present a new synthetic route towards the synthesis of xanthone-1,2,3-triazole dyads 7a-d using consecutively the azide-alkyne Huisgen 1,3-dipolar cycloaddition and Diels-Alder reaction. Our approach involves the synthesis chromone-triazole derivatives 2a-d using the reaction of 1a-d with sodium azide, followed by the methylation of the NH of the triazole moiety. The methylation afforded three isomers 3a-d, 4a-d and 5a-d, as expected. The major isomers 3a-d were used in the Diels-Alder reaction with N-methylmaleimide, and the adducts obtained 6a-d were oxidized to afford the xanthone-1,2,3-triazole dyads 7a-d. All the synthetic details as well as the structural characterization (by 1D and 2D NMR studies) of the new synthesised compounds will be presented and discussed.

Antimicrobial potential of Eucalyptus globulus against biofilms of Staphylococcus aureus isolated from bovine mastitis

Staphylococcus aureus are among the most common species isolated from bovine mastitis. The pathogenesis of this bacterium is facilitated by a number of virulence factors, including the ability to adhere to abiotic surfaces and/or host tissues often leading to biofilms' formation. From the clinical perspective, the most important feature of Staphytococcus species' biofilms is their high tolerance to the conventional antimicrobial therapy. So, the increasing number of bovine mastitis and the higher levels of Staphylococcus species resistance to traditional antimicrobial agents are considered an important alert for the necessity to focus the future research on identification and development of new strategies to combat S. aureus mastitis. RecenUy, the interest in natural alternatives based on plant extracts has been rising. In add~ion to their health benefits, their antimicrobial potential has been increasingly reported. Taking this into consideration, the evaluation of hydromethanolic extracts of E. globulus against S. aureus biofilms was tested and compared with penicillin, one of the antibiotics most often used in the treatment of cattle infections. All mastitis' isolates tested were good-biofilm producers. As expected penicillin has demonstrated poor activity against S. aureus biofilms (<1 log reduction). However, E. globulus Labill was bactericidal, promoting a biofilm cell reduction of 2-3 log. Therefore, the present work showed the potential antimicrobial activity of E. g/obulus against S. aureus from bovine mastitis, namely in biofilm mode of growth and drew attention to its promising use as an alternative to penicillin.