Various species of Basidiomycota fungi reveal different abilities to degrade pharmaceuticals and also different pathways of degradation.

The presence of pharmaceuticals (PhACs) in the aquatic environment is an emerging problem worldwide. PhACs reach surface water via the effluents of wastewater treatment plants (WWTPs). WWTPs, although able to remove organic pollutants, do not always remove PhACs. Currently, in the treatment of sewage with the activated sludge method, numerous microorganisms are used, mostly bacteria. Nevertheless, these microorganisms are not resistant to many drug contaminants, and some may also pose a risk to human health. White-rot fungi (WRF), which degrade a wide spectrum of environmental pollutants, may be used as an alternative to microorganisms. However, little data exists comparing the removal of various PhACs by different WRF. In this study, we aimed to determine the ability of three WRF Basidiomycota species, Armillaria mellea, Phanerochaete chrysosporium, and Pleurotus ostreatus, to remove PhACs from various therapeutic groups over the course of 1 h-4 days. Additionally, we identified the fungal metabolites of PhACs, proposed the degradation pathways, and assessed the toxicity of the post-culture media. All selected WRF removed PhACs, but the degree of removal depended on WRF species and PhACs type. Antidepressants and immunosuppressants were removed most efficiently by P. ostreatus, cardiovascular drugs and sulfamethoxazole by A. mellea, and erythromycin by P. chrysosporium. The vast differences observed highlight the need for more intensive testing of different WRF species to select the best species for removing pharmaceuticals of interest. The structure of metabolites generated during degradation strongly depended on WRF species, but the most frequent xenobiotic transformations were oxidation and dealkylation. The obtained results gave insight into the substrate specificity of selected WRF while also providing a broad extension of the knowledge of pharmaceutical degradation by A. mellea.

Biosynthesis of Se-methyl-seleno-l-cysteine in Basidiomycetes fungus Lentinula edodes (Berk.) Pegler.

BACKGROUND: The aim of the current study was to investigate whether the Basidiomycetes fungus Lentinula edodes can biosynthesize Se-methyl-seleno-l-cysteine, a seleno-amino acid with strong anticancer activity, and to optimize the culture conditions for its biosynthesis. We hypothesize that preparations obtained from Se-methyl-seleno-l-cysteine-enriched mycelia from this medicinal mushroom would possess stronger cancer-preventive properties than current preparations. RESULTS: By optimizing the concentration of selenium in the culture medium, we increased the mycelial concentration of Se-methyl-seleno-l-cysteine from essentially non-detectable levels to 120 µg/g dry weight. Significantly elevated levels of this amino acid also correlated with significant (twofold) inhibition of mycelial growth. Increases in the concentration of mycelial Se-methyl-seleno-l-cysteine appeared to be highly correlated with the enhanced biosynthesis of selenomethionine and total selenium content in mycelium. CONCLUSIONS: We have demonstrated that in L. edodes, enhanced biosynthesis of this non-protein amino acid eliminates excess selenium.

Synthesis of N,N'-bis-substituted diimides related to tricyclo [6.2.2.0(1,6)] dodecane with an expected activity on the central nervous system.

Continuing our studies connected with the design of antipsychotic and anxiolytic agents with a reduced propensity toward extrapyramidal side-effects, the synthesis of new compounds related to 3,7-dimethyltricyclo [6.2.2.0(1,6)] dodecen-6-yl-9,10,11,12-tetracarboxydiimide was performed. The first result of the pharmacological screening test of two of synthesized compounds displayed their low affinity for the serotonin receptor site.

Synthesis of N-(4-aryl-1-piperazinylbutyl)-substituted 7,8-benzo-1,3-diazaspiro[4,5]decane-2,4-dione derivatives with potential anxiolytic activity.

Continuing our studies connected with the design of new anxiolytics we have now synthesized a series of new compounds, derivatives of 7,8-benzo-1,3-diazaspiro[4,5]decane-2,4-dione bearing a 4-aryl-1-piperazinylbutyl group attached to the imide nitrogen. One single compound was submitted to the 5-HT1A receptor binding assay and found to display the expected--though rather weak--receptorial affinity.

Synthesis of new N-substituted benzodiazepine derivatives with potential anxiolytic activity.

In continuation of the development of antipsychotic and anxiolytic agents with a reduced propensity toward extrapyramidal side-effects, a series of N-aminoalkyl derivatives of (s)-(+)-2,3-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11-(10H, 11aH)-dione was prepared. Evaluation of these compounds in revealed a very low affinity for 5-HT1A receptor.

Synthesis of N,N'-bis-aminoalkyl-substituted derivatives of bicyclo[2.2.2]oct-7-ene-2,3,5,6-tetracarboxydiimide with potential anxiolytic activity.

In continuation of the search for discovering new antipsychotic and anxiolytic agents with a reduced production of extrapyramidala side-effects, a series of N,N'-bis-aminoalkyl derivatives of bicyclo[2.2.2]oct-7-ene tetracarboxydiimide was prepared. Evaluation of these compounds in vitro revealed a very low affinity for 5-HT1A receptor.

Synthesis and pharmacological screening of some N,N'-bis-[4-(4-aryl-1-piperazinyl)butyl]-substituted derivatives of 1,8-dimethylbicyclo-[2.2.2]oct-7-ene-2,3,5,6-tetracarboxydiimide.

The preparation of several derivatives of bicyclo[2.2.2]oct-7-ene- 2,3,5,6-tetracarboxydiimide on two routes has been described. Some of them display an expected anxiolytic activity. The 5-HT1A receptor affinities of tested compounds are comparable with that of buspirone.

[Synthesis of new derivatives of 5H-furo[3,2-g][1]benzopyran-5-one with potential beta-adrenolytic activity]. / Synteza nowych pochodnych 5h-furo [3-2-g] [1]-benzopiran-5-onu o spodziewanym dzialaniu beta-adrenolitycznym.

With the purpose of obtaining new compounds with antiarrhythmic activity, nine novel aminoalkanol derivatives of 5H-furo[3,2-g] [1]benzopyran-5-one were synthetized. In pharmacological studies, compound IX proved to display strong antiarrhythmic action, which in chloroform-induced arrhythmia was stronger from that of propranolol at three times lower acute toxicity.

[Synthesis of derivative of 2-[4-hydroxy-7-methyl-5-oxo-5H-furo-[3,2g] [1]benzopyran-9-yloxy] acetic and propionic acids with potential effect on the circulatory system]. / Synteza pochodnych kwasów 2-[4-hydroksy-7-metylo-5-okso-5h-furo [3,2-g] [1] benzopiran-9-yloksy] octowego i propionowego o spodziewanym dzialaniu na uklad krazenia.

With the purpose of obtaining new compounds with antiarrhythmic activity, 14 novel derivatives of 5H-furo[3,2-g] [1]benzopyran-5-one were synthetized. Some of them proved to display strong antiarrhythmic action.