Natural Products from Chilean and Antarctic Marine Fungi and Their Biomedical Relevance.

Fungi are a prolific source of bioactive molecules. During the past few decades, many bioactive natural products have been isolated from marine fungi. Chile is a country with 6435 Km of coastline along the Pacific Ocean and houses a unique fungal biodiversity.

Secondary Metabolites Isolated from Chilean Marine Algae: A Review.

Chile is in the extreme southwestern part of America, and it has an extreme length, of approximately 4300 km that increases to 8000 km considering the Chilean Antarctic Territory. Despite the large extent of its coastal territory and the diversity of geographic environments and climates associated with Chilean coasts, the research on marine resources in Chile has been rather scarce. From marine organisms found in Chilean coastal waters, algae have been the most studied, since they contain a wide range of interesting secondary metabolites that have some structural traits that make them unique and uncharacteristic.

Synthesis, characterisation, crystal structure and antimicrobial evaluation of novel 6-alkoxyergosta-4,6,8(14),22-tetraen-3-one derived from natural ergosta-5,7,22-trien-3β-ol.

In this study, we report a facile transformation starting from 5α-hydroxyergosta-7,22-dien-3,6-dione to afford two novel compounds: 6-methoxyergosta-4,6,8(14),22-tetraen-3-one and 6-ethoxyergosta-4,6,8(14),22-tetraen-3-one ( using alcoholic acid catalysis. Their structures were elucidated using NMR experiments, FT-IR, MS and X-ray analysis. These compounds were evaluated for antibacterial activity using the disk and broth diffusion test.

Antileishmanial activity and cytotoxicity of ent-beyerene diterpenoids.

We describe the in vitro activity of two natural isomeric ent-beyerene diterpenes, several derivatives and synthetic intermediates. Beyerenols 1 and 2 showed EC of 4.6 ± 9.

A set of biogenetically interesting polyhalogenated acetogenins from Ptilonia magellanica.

Ptilonines A-F, pyranosylmagellanicus D-E and magellenediol are previously undescribed acetogenins isolated from the red alga Ptilonia magellanica. Their structures were determined from spectroscopic evidence. The absolute configuration of the known pyranosylmagellanicus A, was established by derivatization with (R)- and (S)-α-methoxy -α-phenylacetic acids (MPA).

Antimicrobial Diterpenes from Azorella Species Against Gram-Positive Bacteria.

The present study was aimed at evaluating the antibacterial activity of mulinane and azorellane diterpenes isolated from the Andean plants Azorella compacta and A. trifoliolata and semisynthetic derivatives against reference and multidrug-resistant strains. The results revealed that the semisynthetic compound 7-acetoxy-mulin-9,12-diene (5) exhibited antibacterial activity against reference and multidrug-resistant strains of Staphylococcus aureus and moderate antimycobacterial activity against Mycobacterium smegmatis ATCC 14468.

Vibrational Circular Dichroism Absolute Configuration of 9,12-Cyclomulin-13-ol, a Diterpene from Azorella and Laretia Species.

The absolute configuration of the diterpenoid 9,12-cyclomulin-13-ol (1), a constituent of Azorella and Laretia species, has been established by vibrational circular dichroism spectroscopy in combination with density functional theory calculations. The obtained normal diterpene absolute configuration confirms that of azorellanol (2), which was determined by single crystal X-ray diffraction.

Molecular Docking Studies of the Antitumoral Activity and Characterization of New Chalcone.

Phytochemical investigation of Azorella madreporica led to the isolation of four known compounds and an unknown chalcone. The structure of the new compound was identified by spectroscopy, including two-dimensional NMR techniques and comparison with published spectral data. The antioxidant activity of chalcone (compound 1) was measured using the 1,2-diphenyl-2-picryl-hydrazyl (DPPH) free radical scavenging assay, and the bioactivity was evaluated against five bacteria (Mycobacterium smegmatis ATCC 14468, clinical isolates of Staphylococcus aureus, Klebsiella granulomatis, Morganella morganii and Escherichia coli) and four cancer cell lines.

An unusual mulinane diterpenoid from the Chilean plant Azorella trifurcata (Gaertn) Pers.

Four new mulinane-type diterpenoids besides the known compounds mulin-11,13-dien-20-oic acid, 13α-hydroxyazorellane, 13β-hydroxyazorellane, mulinolic acid, azorellanol, and mulin-11,13-dien-18-acetoxy-16,20-dioic acid were isolated from the Chilean plant Azorella trifurcata. One of the new metabolites isolated, 7α-acetoxy-9-epi-13β-hydroxymulinane, possesses a new trans-syn-trans arrangement in a tricyclic ring system not previously encountered in nature. Among the mulinane diterpenoids isolated, mulin-11,13-dien-20-oic acid showed the gastroprotective effect on HCl-EtOH-induced gastric lesions in mice (ED50 = 55 mg kg(-1)).

New diterpenes from Azorella spinosa.

Two new diterpenes,2-acetoxy-13-hydroxy-mulin-11-ene and 2-acetoxy-mulin-11, 13-diene,have been isolated from the aerial parts of Azorella spinosa and their structures determined by spectroscopic and conventional chemical methods. Furthermore, 2, 13-dihydroxy-mulin-11-ene was obtained using a basic hydrolysis of the first compound. Two diterpenes reported for other Azorella species have also been found, namely mulinolic acid and 13beta-hydroxyazorellane, as well as the triterpene lactone of ursolic acid,quercetin, and 7-hydroxycoumarin.

Diversity of cultivable fungi associated with Antarctic marine sponges and screening for their antimicrobial, antitumoral and antioxidant potential.

The diversity of sponge-associated fungi has been poorly investigated in remote geographical areas like Antarctica. In this study, 101 phenotypically different fungal isolates were obtained from 11 sponge samples collected in King George Island, Antarctica. The analysis of ITS sequences revealed that they belong to the phylum Ascomycota.

Induction of defensive response in Eucalyptus globulus plants and its persistence in vegetative propagation.

The expression of defensive compounds derived from secondary metabolism in plants of Eucalyptus globulus Labill, and the persistence of these in vegetative propagation was evaluated by gas chromatography with flame ionization (GC-FID) and mass spectrometry (MS). The plants were induced by attack from the insect Ctenarytaina eucalypti ("blue gum psyllid") and by mechanical damage. Defense responses were activated in plants for the different types of tested induction.

Biological activity of isoflavonoids from Azorella madreporica.

Four isoflavones, isolated from the whole plant of Azorella madreporica, were identified as angustone C (1), alpinumisoflavone (2), licoisoflavone A (3) and isolupalbigenin (4) by spectroscopic studies. The compounds were evaluated for antibacterial and gastroprotective activities. This is the first time that isoflavonoids have been reported in this genus.

Molecules of the quinoline family block tau self-aggregation: implications toward a therapeutic approach for Alzheimer's disease.

The neurofibrillary tangles (NFTs) generated by self-aggregation of anomalous forms of tau represent a neuropathological hallmark of Alzheimer's disease (AD). These lesions begin to form long before the clinical manifestation of AD, and its severity is correlated with cognitive impairment in patients. We focused on the search for molecules that interact with aggregated tau of the Alzheimer's type and that may block its aggregation before the formation of NFTs.

Gastroprotective activity of epitaondiol and sargaol.

The effects of epitaondiol (1) and sargaol (2), isolated from the brown alga Stypopodium flabelliforme on HCl/ethanol-induced gastric lesions in mice were evaluated and compared with that of lansoprazole. Epitaondiol and sargaol (6.25 - 50 mg/kg) dose-dependently inhibited the appearance of gastric lesions in mice, displaying similar values to lansoprazole at 20 mg/kg.

Anti-proliferative activity of meroditerpenoids isolated from the brown alga Stypopodium flabelliforme against several cancer cell lines.

The sea constitutes one of the most promising sources of novel compounds with potential application in human therapeutics. In particular, algae have proved to be an interesting source of new bioactive compounds. In this work, six meroditerpenoids (epitaondiol, epitaondiol diacetate, epitaondiol monoacetate, stypotriol triacetate, 14-ketostypodiol diacetate and stypodiol) isolated from the brown alga Stypopodium flabelliforme were tested for their cell proliferation inhibitory activity in five cell lines.

A new azorellane diterpenoid from Azorella madreporica.

A new azorellane diterpenoid has been isolated and identified from the aerial parts of Azorella madreporica Clos. The structure of 1 was established by one- and two-dimensional NMR techniques.

Microbial transformation of marine halogenated sesquiterpenes.

The sesquiterpene pacifenol is one of the main constituents of the red alga Laurencia claviformis. Earlier work on the semisynthetic derivatives of pacifenol afforded a series of halogenated sesquiterpenes. The aim of the present work was to obtain new hydroxylated derivatives of halogenated sesquiterpenes by means of microbial transformation using Aspergillus niger, Gibberella fujikuroi and Mucor plumbeus.

Diterpenoids from Azorella madreporica and their antibacterial activity.

Two new diterpenoids, mulin-12-en-16-al-20-oic acid and 13-α-hydroxy-mulin-11-en-14-one-20-oic acid, were isolated from Azorella madreporica. Their structures were identified on the basis of one-dimensional and two-dimensional NMR experiments. Their antibacterial activity was also tested.

Stereostructure reassignment and absolute configuration of isoepitaondiol, a meroditerpenoid from Stypopodium flabelliforme.

Careful examination of the published NMR data for isoepitaondiol, a meroditerpenoid from Stypopodium flabelliforme, suggests that its published structure 1 must be revised. On the basis of extensive 1D and 2D NMR studies, we now propose that structure 2, with a trans-anti-trans-anti-cis arrangement fits isoepitaondiol diacetate. The relative configuration of 2 was confirmed by single-crystal X-ray diffraction, while the absolute configuration was evidenced by vibrational circular dichroism in combination with DFT B3LYP/DGDZVP calculations.

Diastereoisomeric assignment in a pacifenol derivative using vibrational circular dichroism.

The configuration of a chiral center in semisynthetic (-)-(2R,5R,5aR,8zeta,9aS)- 2,8-dibromo-2,5,9,9a-tetrahydro-5-hydroxy-5,8,10,10-tetramethyl-6H-2,5a-methano-1-benzoxepin-7(8H)-one (3 or 4), prepared in two steps from (-)-(2R,5R,5aR,7S,8S,9aS)-2, 7-dibromo-8-chloro-2,5,7,8,9,9a-hexahydro-5,8,10,10-tetramethyl-6H-2,5a-methano-1-benzoxepin-5-ol, known as pacifenol 1, has been determined using vibrational circular dichroism (VCD) measurements. The vibrational spectra (IR and VCD) of diastereoisomers 3 and 4 were calculated using density functional theory (DFT) at the B3LYP/DGDZVP level of theory for the two conformers that in each case account for the total energetic distribution found in the first 10 kcal/mol range. The DFT conformational optimization of the 8R diastereoisomer 3 indicates the cyclohexanone exists almost exclusively in a boat conformation with a beta-equatorial bromine atom and an alpha-axial methyl group at the chiral center alpha to the carbonyl group, while for the 8S diastereoisomer 4 a 5:1 conformational distribution in favor of a chair conformation with an alpha-axial bromine atom and a beta-equatorial methyl group is calculated, suggesting due to well-known chair versus boat relative stabilities that the plausible diastereoisomer would be the 8S molecule.

VCD determination of the absolute configuration of stypotriol.

The absolute configuration of the pentacyclic ichthyotoxin stypotriol, a constituent of Stypopodium zonale, was deduced to be 3S,5R,8R,9R,10S,13S,14S-(-)-1 by vibrational circular dichroism spectroscopy of the derived triacetate 2 in comparison to DFT B3LYP/DGDZVP calculations. Compound 2, C33H46O7 having 300 electrons, is the largest natural product successfully studied by VCD to date.

An unusual halogenated meroditerpenoid from Stypopodium flabelliforme: studies by NMR spectroscopic and computational methods.

Meroditerpenoids, 2-[2'(E)-3',7',11',15'-tetramethylhexadec-2-en-1'-yl]-6-methyl-1,4-benzohydroquinone diacetate and 4'-chlorostypotriol triacetate, along with eight known compounds isolated from the dichloromethane extract of the brown alga Stypopodium flabelliforme after peracetylation are reported. One of them, 2-(1-oxo-hexadecyl)-1,3,5-trihydroxybenzene, is described for the first time within this genus. Structural elucidation was carried out on the basis of spectroscopic data and theoretical studies using GIAO/DFT analysis at B3LYP/6-31G(d) and mPW1PW91/6-31G(d) levels of theory for 4'-chlorostypotriol.

Antituberculosis activity of natural and semisynthetic azorellane and mulinane diterpenoids.

The antituberculosis activity of 14 natural azorellane and mulinane diterpenoids isolated from Azorella compacta, Azorella madreporica, Mulinum crassifolium, and Laretia acaulis, together with eight semisynthetic derivatives, was evaluated against two Mycobacterium tuberculosis strains. The natural azorellanes azorellanol (3) and 17-acetoxy-13-alpha-hydroxyazorellane (6), and the semisynthetic mulinanes 13-hydroxy-mulin-11-en-20-oic-acid methyl ester (13) and mulinenic acid methyl ester (23), showed the strongest activity, with MIC values of 12.5 microg/mL against both strains.