The presence of fungi in pristine Antarctic soils is of particular interest because of the diversity of this microbial group. However, the extreme conditions that coexist in Antarctica produce a strong selective pressure that could lead to the evolution of novel mechanisms for stress tolerance by indigenous microorganisms. For this reason, in recent years, research on cold-adapted microorganisms has increased, driven by their potential value for applications in biotechnology. Cold-adapted fungi, in particular, have become important sources for the discovery of novel bioactive secondary metabolites and enzymes. In this study, we studied the fungal community structure of 12 soil samples from Antarctic sites, including King George Island (including Collins Glacier), Deception Island and Robert Island. Culturable fungi were isolated and described according to their morphological and phenotypical characteristics, and the richness index was compared with soil chemical properties to describe the fungal community and associated environmental parameters. We isolated 54 fungal strains belonging to the following 19 genera: Penicillium, Pseudogymnoascus, Lambertella, Cadophora, Candida, Mortierella, Oxygenales, Geomyces, Vishniacozyma, Talaromyces, Rhizopus, Antarctomyces, Cosmospora, Tetracladium, Leptosphaeria, Lecanicillium, Thelebolus, Bjerkandera and an uncultured Zygomycete. The isolated fungi were comprised of 70% Ascomycota, 10% Zygomycota, 10% Basidiomycota, 5% Deuteromycota and 5% Mucoromycota, highlighting that most strains were associated with similar genera grown in cold environments. Among the culturable strains, 55% were psychrotrophic and 45% were psychrophilic, and most were Ascomycetes occurring in their teleomorph forms. Soils from the Collins Glacier showed less species richness and greater species dominance compared with the rest of the sites, whereas samples 4, 7, and 10 (from Fildes Bay, Coppermine Peninsula and Arctowski Station, respectively) showed greater species richness and less species dominance. Species richness was related to the C/N ratio, whereas species dominance was inversely related to C and N content. Thus, the structure of the fungal community was mainly related to soil chemical parameters more than sample location and altitude.

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Alzheimer’s disease (AD) is associated with marked atrophy of the cerebral cortex and accumulation of amyloid plaques and neurofibrillary tangles. Amyloid plaques are formed by oligomers of amyloid-β (Aβ) in the brain, with a length of 42 and 40 amino acids. α-secretase cleaves amyloid-β protein precursor (AβPP) producing the membrane-bound fragment CTFα and the soluble fragment sAβPPα with neuroprotective activity; β-secretase produces membrane-bound fragment CTFβ and a soluble fragment sAβPPβ. After α-secretase cleavage of AβPP, γ-secretase cleaves CTFα to produce the cytoplasmic fragment AICD and P3 in the non-amyloidogenic pathway. CTFβ is cleaved by γ-secretase producing AICD as well as Aβ in amyloidogenic pathways. In the last years, the study of natural products and synthetic compounds, such as α-secretase activity enhancers, β-secretase inhibitors (BACE-1), and γ-secretase activity modulators, have been the focus of pharmaceuticals and researchers. Drugs were improved regarding solubility, blood-brain barrier penetration, selectivity, and potency decreasing Aβ42. In this regard, BACE-1 inhibitors, such as Atabecestat, NB-360, Umibecestat, PF-06751979, Verubecestat, LY2886721, Lanabecestat, LY2811376, and Elenbecestat, were submitted to phase I-III clinical trials. However, inhibition of Aβ production did not recover cognitive functions or reverse the disease. Novel strategies are being developed, aiming at a partial reduction of Aβ production, such as the development of γ-secretase modulators or α-secretase enhancers. Such therapeutic tools shall focus on slowing down or minimizing the progression of neuronal damage. Here, we summarize structures and the activities of the latest compounds designed for AD treatment, with remarkable in vitro, in vivo, and clinical phase activities.

The alkaloids aristoteline (1), aristoquinoline (2), and aristone (3) were purified from the leaves of the Maqui tree Aristotelia chilensis and chemically characterized by NMR spectroscopy. The pharmacological activity of these natural compounds was evaluated on human (h) α3β4, α4β2, and α7 nicotinic acetylcholine receptors (AChRs) by Ca2+ influx measurements. The results suggest that these alkaloids do not have agonistic, but inhibitory, activity on each receptor subtype. The obtained IC50 values indicate the following receptor selectivity: hα3β4 > hα4β2 ≫ hα7. In the particular case of hα3β4 AChRs, 1 (0.40 ± 0.20 μM) and 2 (0.96 ± 0.38 μM) show higher potencies compared with 3 (167 ± 3 μM). Molecular docking and structure–activity relationship results indicate that ligand lipophilicity is important for the interaction with the luminal site located close to the cytoplasmic side of the hα3β4 ion channel between positions -2′ and -4′. Compound 1 could be used as a molecular scaffold for the development of more potent noncompetitive inhibitors with higher selectivity for the hα3β4 AChR that could serve for novel addiction and depression therapies.

Due to the increasing emergence of resistance of bacterial pathogens to current antibiotics, we have examined the marine fungi present in sea sediments obtained 200 m offshore to discover new antibacterial compounds active against multidrug-resistant bacteria. One strain, identified as Emericellopsis minima, was isolated from sediments of Talcahuano Bay (Chile). From the liquid culture of E. minima, we isolated Emerimicin IV, a unique fungal peptaibol that exhibited antibacterial activity. The structure of this compound was assigned by interpretation of H NMR and HR-LCMS data. Emerimicin IV showed bacteriostatic activity against clinical isolates of methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis with MIC values ranging between 100 and 12.5 μg/mL.

The drimane sesquiterpenoids drimenin, cinnamolide, dendocarbin A, and polygodial were purified from the Canelo tree ( Drimys winteri) and chemically characterized by spectroscopic methods. The pharmacological activity of these natural compounds were determined on hα4β2, hα3β4, and hα7 nicotinic acetylcholine receptors (AChRs) by Ca influx measurements. The results established that drimane sesquiterpenoids inhibit AChRs with the following selectivity: hα4β2 > hα3β4 > hα7. In the case of hα4β2 AChRs, the following potency rank order was determined (IC's in μM): drimenin (0.97 ± 0.35) > cinnamolide (1.57 ± 0.36) > polygodial (62.5 ± 19.9) ≫ dendocarbin A (no activity). To determine putative structural features underlying the differences in inhibitory potency at hα4β2 AChRs, additional structure-activity relationship and molecular docking experiments were performed. The Ca influx and structural results supported a noncompetitive mechanism of inhibition, where drimenin interacted with luminal and nonluminal (TMD-β2 intrasubunit) sites. The structure-activity relationship results, i.e., the lower the ligand polarity, the higher the inhibitory potency, supported the nonluminal interaction. Ligand binding to both sites might inhibit the hα4β2 AChR by a cooperative mechanism, as shown experimentally ( n > 1). Drimenin could be used as a molecular scaffold for the development of more potent inhibitors with higher selectivity for the hα4β2 AChR.

No abstract

Chagas disease is a neglected tropical disease that is caused by the protozoan Trypanosoma cruzi and represents a serious health problem, especially in Latin America. The clinical treatment of Chagas disease is based on two nitroderivatives that present severe side effects and important limitations. In folk medicine, natural products, including sesquiterpenoids, have been employed for the treatment of different parasitic diseases. In this study, the trypanocidal activity of compounds isolated from the Chilean plants Drimys winteri, Podanthus mitiqui and Maytenus boaria on three T. cruzi evolutive forms (epimastigote, trypomastigote and amastigote) was evaluated. Total extracts and seven isolated sesquiterpenoids were assayed on trypomastigotes and epimastigotes. Polygodial (Pgd) from D. winteri, total extract from P. mitiqui (PmTE) and the germacrane erioflorin (Efr) from P. mitiqui were the most bioactive substances. Pgd, Efr and PmTE also presented strong effects on intracellular amastigotes and low host toxicity. Many ultrastructural effects of these substances, including reservosome disruption, cytosolic vacuolization, autophagic phenotype and mitochondrial swelling (in the case of Pgd), were observed. Flow cytometric analysis demonstrated a reduction in mitochondrial membrane potential in treated epimastigotes and an increase in ROS production and high plasma membrane permeability after treatment with Pgd. The promising trypanocidal activity of these natural sesquiterpenoids may be a good starting point for the development of alternative treatmentsforChagas disease.