Natural Occurring Phenolic Derivatives from Mauritia flexuosa (Buriti) Stems and Their Potential Antibacterial Activity against Methicillin-Resistant Staphylococcus aureus (MRSA).

Mauritia flexuosa Linnaeus filius (buriti or aguage; Arecaceae) is a palm used by traditional medicine in Brazil to treat dysentery and diarrhea. Our group showed that the soluble dichloromethane (CH2 Cl2 ) fraction from EtOH extract from M. flexuosa stems inhibited the growth of methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) and it is rich in phenolic compounds. This study aimed to isolate new phenolic compounds from CH2 Cl2 fraction from M. flexuosa stems with in vitro antibacterial activity. The crude CH2 Cl2 fraction was fractionated by gel permeation chromatography (GPC) followed by semi-preparative RP-HPLC. The antibacterial activity was evaluated using the broth microdilution method against MSSA (ATCC 29213) and MRSA (clinical isolate 155). All compounds were also tested against Gram-negative (Escherichia coli; ATCC 35218) bacteria and two fungi species (Candida albicans; ATCC 14053 and Trichophyton rubrum; ATCC MYA 4438). The chemical structures of isolated compounds were determined by analysis and comparison with literature data of their NMR and HRMS spectra and optical activity. The chemical investigation yielded seven aromatic compounds, of which four, (2S,15S)-2,15-dimethyl-2,15-dioxa-1,8(1,4)-dibenzenacyclotetradecaphane (1), (2S,5S)-1-(4-hydroxyphenyl)hexane-2,5-diol (3), bruguierol E (4), and buritin (5) were previously unreported and three are known compounds identified as 6-(4'-hydroxyphenyl) hexan-2-one (2), (+)-(2R,3R)-dihydrokaempferol (6), and (+)-(2R)-naringenin (7). Compounds 1 and 7 showed antibacterial activity against MRSA and MSSA with minimum inhibitory concentrations (MICs) of between 62.5 and 31.3 µg/mL, respectively. Our preliminary findings support that CH2 Cl2 fraction from buriti, a typical species of flooded areas of Brazilian savanna, and its aromatic phenolic compounds are active against MSSA and MRSA contributing with understanding about the traditional use of this species.

Fungi in glacial ice of Antarctica: diversity, distribution and bioprospecting of bioactive compounds.

We identified cultivable fungi present in the glacial ice fragments collected in nine sites across Antarctica Peninsula and assessed their abilities to produce bioactive compounds. Three ice fragments with approximately 20 kg were collected, melted and 3 L filtered through of 0.45 µm sterilized membranes, which were placed on the media Sabouraud agar and minimal medium incubated at 10 °C. We collected 66 isolates classified into 27 taxa of 14 genera. Penicillium palitans, Penicillium sp. 1, Thelebolus balaustiformis, Glaciozyma antarctica, Penicillium sp. 7, Rhodotorula mucilaginosa, and Rhodotorula dairenensis had the highest frequencies. The diversity and richness of the fungal community were high with moderate dominance. Penicillium species were present in all samples, with Penicillium chrysogenum showing the broadest distribution. P. chrysogenum, P. palitans, and Penicillium spp. had trypanocidal, leishmanicidal, and herbicidal activities, with P. chrysogenum having the broadest and highest capability. 1H NMR signals revealed the presence of highly functionalized secondary metabolites in the bioactive extracts. Despite extreme environmental conditions, glacial ice harbours a diverse fungal community, including species never before recorded in the Arctic and Antarctica. Among them, Penicillium taxa may represent wild fungal strains with genetic and biochemical pathways that may produce new secondary bioactive metabolites.

A new insight into purinergic pharmacology: Three fungal species as natural P2X7R antagonists.

P2X7 is a purinergic receptor involved in important physiological functions and pathological processes, such as inflammation, neurodegeneration, and pain. Despite its relevance, there is no selective antagonist useful in the treatment of diseases related to this receptor. In this context, research for a selective, safe, and potent antagonist compound that can be used in clinical therapy has been growing. In this work, we evaluated the potential antagonistic activity of three fungal extracts, namely, Vishniacozyma victoriae, Metschnikowia australis, and Ascomycota sp., which were discovered in a high-throughput screening campaign to search for new antagonists for P2X7R from natural products. First, the IC50 values of these fungal extracts were determined in J774.G8 (murine macrophage cell line) and U937 (human monocyte cell line) cells through dye uptake assays. The IC50 values of V. victoriae were 2.6 and 0.92 µg/mL, M. australis has IC50 values of 3.8 and 1.5 µg/mL, and Ascomycota sp. showed values of 2.1 and 0.67 µg/mL in J774.G8 and U937 cells, respectively. These extracts also significantly inhibited propidium iodide and Lucifer yellow uptake via P2X7R pore, P2X7R currents in electrophysiology, IL-1ß release, and the production of oxide nitric and reactive oxygen species. The extracts did not cause cytotoxicity within a period of 24 h. The results showed the promising antagonistic activity of these extracts toward P2X7R, thereby indicating that they can be future candidates for phytomedicines with potential clinical applicability.

Altenusin, a biphenyl isolated from the endophytic fungus Alternaria sp., inhibits trypanothione reductase from Trypanosoma cruzi.

Parasitic protozoan species belonging to the genera Trypanosoma and Leishmania are the etiological agents of several diseases in tropical areas of the world, for which there is an urgent need for effective and affordable treatment. In this regard, we are screening the Brazilian biodiversity, especially its flora and mycota, for natural products that could serve as leads for drug development against these diseases. Trypanothione reductase (TR) is an enzyme involved in the protection of Trypanosoma and Leishmania species against oxidative stress, and is considered to be a validated drug target. The endophytic fungus Alternaria sp. (UFMGCB55) was isolated from the plant Trixis vauthieri DC (Asteraceae), known to contain trypanocidal compounds. The organic extract of the culture of Alternaria sp. was able to inhibit TR by 99%, when tested at 20 microg mL(-1). Fractionation of the extract identified altenusin, a biphenyl derivative with an IC50 value of 4.3+/-0.3 microM in the TR assay. This compound is the first in its class to have shown TR inhibitory activity, opening new perspectives for the design of more effective derivatives that could serve as drug leads for new chemotherapeutic agents to treat trypanosomiasis and leishmaniasis.