benzofurans and depsidone

Lichen metabolites exert a wide variety of biological actions including antibiotic, antimycobacterial, antiviral, antiinflammatory, analgesic, antipyretic, antiproliferative and cytotoxic effects. Even though these manifold activities of lichen metabolites have now been recognized, their therapeutic potential has not yet been fully explored and thus remains pharmaceutically unexploited. In this mini-review, particular attention is paid to the most common classes of small-molecule constituents of lichens, from both the chemical viewpoint and with regard to possible therapeutic implications. In particular, aliphatic acids, pulvinic acid derivatives, depsides and depsidones, dibenzofuans, anthraquinones, naphthoquinones as well as epidithiopiperazinediones are described. An improved access to these lichen substances in drug discovery high-throughput screening programs will provide impetus for identifying novel lead-compounds with therapeutic potential and poses new challenges for medicinal chemistry.

Topics: 4-Butyrolactone; Anthraquinones; Benzofurans; Depsides; Hydroxybenzoates; Lactones; Lichens; Naphthoquinones

Natural products from lichens are widely investigated for their biological properties, yet their potential as central nervous system (CNS) therapeutic agents is less explored.. The present study investigated the neuroactive properties of selected lichen compounds (atranorin, perlatolic acid, physodic acid and usnic acid), for their neurotrophic, neurogenic and acetylcholine esterase (AChE) activities.. Neurotrophic activity (neurite outgrowth) was determined using murine neuroblastoma Neuro2A cells. A MTT assay was performed to assess the cytotoxicity of compounds at optimum neurotrophic activity. Neuro2A cells treated with neurotrophic lichen compounds were used for RT-PCR to evaluate the induction of genes that code for the neurotrophic markers BDNF and NGF. Immunoblotting was used to assess acetyl H3 and H4 levels, the epigenetic markers associated with neurotrophic and/or neurogenic activity. The neurogenic property of the compounds was determined using murine hippocampal primary cultures. AChE inhibition activity was performed using a modified Ellman's esterase method.. Lichen compounds atranorin, perlatolic acid, physodic acid and (+)-usnic acid showed neurotrophic activity in a preliminary cell-based screening based on Neuro2A neurite outgrowth. Except for usnic acid, no cytotoxic effects were observed for the two depsides (atranorin and perlatolic acid) and the alkyl depsidone (physodic acid). Perlatolic acid appears to be promising, as it also exhibited AChE inhibition activity and potent proneurogenic activity. The neurotrophic lichen compounds (atranorin, perlatolic acid, physodic acid) modulated the gene expression of BDNF and NGF. In addition, perlatolic acid showed increased protein levels of acetyl H3 and H4 in Neuro2A cells.. These lichen depsides and depsidones showed neuroactive properties in vitro (Neuro2A cells) and ex vivo (primary neural stem or progenitor cells), suggesting their potential to treat CNS disorders.

Topics: Acetylcholinesterase; Animals; Benzoates; Benzofurans; Biological Products; Brain-Derived Neurotrophic Factor; Cell Line; Central Nervous System; Central Nervous System Diseases; Cholinesterase Inhibitors; Depsides; Dibenzoxepins; Gene Expression; Hydroxybenzoates; Lactones; Lichens; Mice; Nerve Growth Factor; Neural Stem Cells; Neurogenesis

Usnea undulata Stirton (Usneaaceae) is a fruticose lichen used locally in ethnoveterinary medicine to treat mammary infections in cattle while human beings use it for the treatment of wounds in Eastern Cape, South Africa. Bioactivity-guided fractionation of its extracts led to the isolation and characterization of a new depsidone, 2'-O-methylhypostictic acid (8), together with seven known compounds, i.e. methyl β-orsellinate, norstictic acid, menegazziaic acid, (+) usnic acid, hypoconstictic acid, salazinic acid, and galbinic acid. The structures of the compounds were elucidated on the basis of their spectral analysis including homo- and hetero-nuclear correlation NMR experiments (COSY, NOESY, HMQC, and HMBC) and mass spectra as well as by comparison with available data in the literature. The minimum inhibitory concentrations (MICs) values of the compounds against six bacteria were determined. Compound 8 showed inhibitory activity against Bacillus cereus, Bacillus subtilis, and Staphylococcus epidermidis with MICs of 31, 62.5, 62.5 μg/ml, respectively. (+) Usnic acid was most active against B. subtilis, B. cereus, Staphylococcus aureus, and Escherichia coli with MICs of 8, 8, 31, and 31 μg/ml, respectively, while other compounds exhibited moderate activity.

Topics: Animals; Anti-Bacterial Agents; Bacillus cereus; Bacillus subtilis; Benzofurans; Cattle; Depsides; Escherichia coli; Humans; Lactones; Microbial Sensitivity Tests; Salicylates; South Africa; Staphylococcus aureus; Usnea

Two new depsidones, livistones A (1) and B (2), and a new benzofurane, livistone C (3), together with the 11 known compounds including three stilbenes (4-6), four steroids, three flavan-3-ols, and an alkaloid were isolated from the fruits of Livistona chinensis. The structures of the new compounds were determined by spectroscopic methods. Compounds 1, 4-6 exhibited remarkable cell protective activities against H(2)O(2)-induced SH-SY5Y cell damage.

Topics: Alkaloids; Arecaceae; Benzofurans; Depsides; Drug Screening Assays, Antitumor; Drugs, Chinese Herbal; Fruit; Humans; Hydrogen Peroxide; Lactones; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Oxepins; Phenols; Phytosterols; Stereoisomerism; Stilbenes

There are a large number of species of Antarctic lichens, and several studies describing the secondary metabolites present in these lichens, as well as the advances in understanding the chemistry of these metabolites, have been reported. In addition, some derivatives displaying interesting antibacterial effects have been described. The cytotoxic and apoptotic effects of 15 secondary metabolites (depsides, depsidones and usnic acid) obtained from Continental (Chilean) and Antarctic lichens were evaluated in primary cultures of rat hepatocytes. Intracellular lactate dehydrogenase release, caspase 3 activation and DNA fragmentation were measured. In this study, we have evaluated a set of markers associated with pivotal steps in the execution phase of apoptosis, in order to detect compounds with apoptotic effects on hepatocytes before significant necrosis takes place. Flow cytometric analysis of DNA fragmentation revealed an increase in apoptotic nuclei with sub-diploid DNA content after the exposure of hepatocytes to sub-cytotoxic concentrations of the compounds. Among these, salazinic acid, stictic acid and psoromic acid displayed significant apoptotic activities.

Topics: Animals; Antarctic Regions; Apoptosis; Benzoates; Benzofurans; Carboxylic Acids; Caspase 3; Caspases; Depsides; Enzyme Activation; Flow Cytometry; Hepatocytes; Hydroxybenzoates; Lactones; Lichens; Male; Rats; Rats, Sprague-Dawley