Auranofin is an effective agent against clinical isolates of Staphylococcus aureus.

Aim: The orphan drug auranofin was recently found to exhibit antimicrobial properties. Materials & methods: We explored the efficacy of auranofin by evaluating the minimal inhibitory concentration against a collection of over 500 clinical isolates derived from multiple institutions, inclusive of drug resistant strains. Our evaluation also included continuous exposure of bacteria to auranofin. Results & conclusion: We found that minimal inhibitory concentrations ranged between 0.125 and 1 mg/l, exerting robust antimicrobial activity against a sizeable clinical collection of the bacteria. Further, we evaluated the propensity of the methicillin-resistant Staphylococcus aureus strain MW2 to develop resistance through extended exposure to auranofin. After 25 days, the bacteria remained susceptible. Our data suggest that resistance mechanisms do not currently exist to block auranofin antimicrobial activity.

Synthesis and Evaluation of Antifungal and Antitrypanosomastid Activities of Symmetrical 1,4-Disubstituted-1,2,3-Bistriazoles Obtained by CuAAC Conditions.

BACKGROUND: The trypanosomatids, such as the protozoan Leishmania spp., have a demand by ergosterol, which is not present in the membrane from mammal cells. The suppression of the synthesis of ergosterol would be a new target of compounds with leishmanicidal activity, and bistriazole has shown trypanocidal activity by this mechanism. The incidence of fungal infections has increased at an alarming rate over the last decades. This is related both to the growing population of immune-compromised individuals and to the emergence of strains that are resistant to available antifungals. Therefore, there is a challenge for the search of potential new antifungal agents. OBJECTIVE: The study aimed to synthesize 1,4-disubstituted-1,2,3-bistriazoles by optimized copper( I)-catalyzed alkyne-azide cycloaddition (CuAAC) and evaluate their antifungal and antitrypanosomastid activities. METHOD: The synthesis of symmetrical bistriazoles with diazides as spacers was planned to be performed following the CuAAC reaction strategy. For evaluation of best conditions for the synthesis of symmetrical bistriazoles hex-1-yne 2 was chosen as leading compound, and a variety of catalysts were employed, choosing (3:1) alkyne:diazide stoichiometric relationship employing CuSO4.5H2O as the best condition. For the preparation of diversity in the synthesis of symmetrical bistriazoles, a 1,3-diazide-propan-2-ol 1a and 1,3-diazidepropane 1b were reacted with seven different alkynes, furnishing eleven symmetrical bistriazoles 9-13a,b and 14a. All compounds were essayed to cultures of promastigotes of L. amazonensis (1 x 106 cells mL-1) in the range of 0.10 - 40.00 µg mL-1 and incubated at 25ºC. After 72 h of incubation, the surviving parasites were counted. For antifungal assay, the minimum inhibitory concentrations (MIC) for yeasts and filamentous fungi were determined. Each compound was tested in 10 serial final concentrations (64 to 0.125 µg mL-1). RESULTS: Eleven 1,4-disubstituted-1,2,3-bistriazoles were synthesized and their structures were confirmed by IR, 1H and 13C-NMR and Mass spectral analysis. The antifungal and antitrypanosomastid activities were evaluated. The best result to antifungal activity was reached by bistriazole 11a that showed the same MIC of fluconazole (32 µg mL-1) against Candida krusei ATCC 6258, an emerging and potentially multidrug-resistant fungal pathogen. Due to their intrinsically biological activity versatility, five derivatives compounds showed leishmanicidal inhibitory activity between 15.0 and 20.0% at concentrations of 20 and 40.0 µg mL-1. Among these compounds the derivative 13a showed best IC50 value of 63.34 µg mL-1 (182.86 µM). CONCLUSION: The preliminary and promising results suggest that bistriazole derivatives, especially compound 13a, could represent an innovative scaffold for further studies and development of new antifungal and anti-parasitic drug candidates.

Invasion of the Brazilian campo rupestre by the exotic grass Melinis minutiflora is driven by the high soil N availability and changes in the N cycle.

The Serra do Rola Moça State Park (PESRM) in Minas Gerais State, Brazil is a preserved site representative of the campo rupestre biome over an ironstone outcrop that has a high level of plant diversity. Almost 60% of this grassy field has been invaded by the exotic molasses grass (Melinis minutiflora), which constitutes a severe threat to the biodiversity and survival of this biome, particularly due to the impacts of annual fires and inappropriate restoration interventions. Many invasive species exhibit a high demand for nitrogen (N). Hence, this work aimed to study the N cycle alterations promoted by M. minutiflora in a site of the campo rupestre, where the leguminous species Mimosa pogocephala was prevalent. The biome's soils exhibited a high natural N fertility and low C:N ratio. The main N source in this biome resulted from the biological N fixation performed by M. pogocephala associated with Burkholderia nodosa, as evidenced by the total leaf N content, leaf δ15N signature, nodule occupation and bacterial molecular identification analyses. The displacement of native species by molasses grass was associated with changes in the soil N forms, namely the nitrate increased as the ammonium decreased. The latter was the dominant N form in the native species plots, as observed in the soil analysis of total N, ammonium and nitrate contents. The dominant ammonium form was changed to the nitric form by the stimulation of ammonia-oxidising bacteria populations due to the invasive species. Therefore, the key mechanism behind the invasiveness of the exotic grass and the concomitant displacement of the native species may be associated with changes in the soil N chemical species. Based on this finding and on the high N-based soil fertility found in the campo rupestre N fertilisation procedures for restoration of invaded areas should be strictly avoided in this biome.

Synthesis of aryl aldimines and their activity against fungi of clinical interest.

Aldimines are aldehyde-derived compounds that contain a C=N group. Besides its broad industrial applications, this class of non-naturally occurring compounds are found to possess antibacterial, antifungal, antimalarial, antiproliferative, anti-inflammatory, antiviral, and antipyretic properties. Based on this, six aryl aldimines were synthesized from the condensation of aromatic amines with benzaldehydes. The antifungal activities of synthesized compounds were evaluated against nineteen fungal strains that included Candida and Aspergillus species, Cryptococcus neoformans. The aryl aldimines 2-(benzylideneamino)phenol (3) and 4-(benzylideneamino)phenol (8) were the most active compounds against the fungi studied. Compounds 3 and 8 efficiently inhibited the metabolism of C. neoformans mature biofilm.