benzofurans and gyrophoric-acid

A series of lichen secondary metabolites (parietin, atranorin, usnic and gyrophoric acid) and their interactions with calf thymus DNA were investigated using molecular biophysics and biochemical methods. The binding constants K were estimated to range from 4.3×10(5) to 2.4×10(7)M(-1) and the percentage of hypochromism was found to be 16-34% (from spectral titration). The results of spectral measurement indicate that the compounds act as effective DNA-interacting agents. Electrophoretic separation studies prove that from all the metabolites tested in this study, only gyrophoric acid exhibited an inhibitory effect on Topo I (25μM).

Topics: Animals; Benzoates; Benzofurans; Cattle; Circular Dichroism; DNA; Emodin; Humans; Hydroxybenzoates; Intercalating Agents; Kinetics; Lichens; Nucleic Acid Conformation; Spectrophotometry, Ultraviolet; Topoisomerase I Inhibitors; Topoisomerase II Inhibitors

Three lichen extracts and ten lichenic compounds have been screened for their photoprotective activities. The determination of their Sun Protection Factor (SPF) and Protection Factor-UVA (PF-UVA) values was done in vitro. Among them, a Lasallia pustulata extract and gyrophoric acid exhibited SPF values over 5, which is better than Homosalate (SPF≈4). Their photoprotective properties are only slightly modified after a 2-hours period of irradiation. Salazinic acid and L. pustulata presented characteristics of a UVA booster like the butyl-methoxydibenzoylmethane (Avobenzone) (PF-UVA≈2 vs. 2.8 for Avobenzone). Salazinic acid was a better anion superoxide scavenger than ascorbic acid and none of them exhibited a photosensitizing cytotoxicity by exposing them on HaCaT cells to UVA radiations (photo-irritancy factor PIF<5).

Topics: Antioxidants; Ascomycota; Benzoates; Benzofurans; Cell Line; Fumarates; Humans; Lactones; Salicylates; Sun Protection Factor; Ultraviolet Rays; Usnea

The larvicidal activity of some lichen metabolites, (+)-usnic acid, atranorin, 3-hydroxyphysodic acid and gyrophoric acid, against the second and third instar larvae of the mosquito Culiseta longiareolata were studied. All metabolites caused high larvicidal activities. When metabolites were compared on the basis of their LC(50) values, the order of increasing toxicity was as follows: gyrophoric acid (0.41 ppm) > (+)-usnic acid (0.48 ppm) > atranorin (0.52 ppm) > 3-hydroxyphysodic acid (0.97 ppm). However, when LC(90) values were compared, the order of toxicity was (+)-usnic acid (1.54 ppm) > gyrophoric acid (1.93 ppm) > 3-hydroxyphysodic acid (4.33 ppm) > atranorin (5.63 ppm). In conclusion, our results found that lichen secondary metabolites may have a promising role as potential larvicides.

Topics: Animals; Benzoates; Benzofurans; Culicidae; Dibenzoxepins; Hydroxybenzoates; Insecticides; Larva; Lethal Dose 50; Lichens; Molecular Structure

One of the ways for searching for potentially new anti-cancer drugs is the testing of various naturally synthesized compounds. Lichens are a source of unique chemical agents of which some have already been proved to be effective against various cancer in vitro models. Our study reports on the sensitivity of up to nine human cancer cell lines (A2780, HeLa, MCF-7, SK-BR-3, HT-29, HCT-116 p53(+/+), HCT-116 p53(-/-), HL-60 and Jurkat) to the anti-proliferative/cytotoxic effects of four typical secondary metabolites of lichens (parietin, atranorin, usnic acid and gyrophoric acid). Variations in the dynamics of tumour cell line populations were evaluated by the MTT, clonogenic and viability assays, cell proliferation and detachment, cell cycle transition and apoptotic nuclear morphology, thereby confirming their concentration- and time-dependent cytotoxicity. However, in comparison with parietin and gyrophoric acid, the suppression of viability and cell proliferation by usnic acid or atranorin was found to be more efficient at equitoxic doses and correlated more strongly with an increased number of floating cells or a higher apoptotic index. Moreover, the analysis of cell cycle distribution also revealed an accumulation of cells in S-phase. This study has confirmed a differential sensitivity of cancer cell lines to lichen secondary metabolites.

Topics: Antineoplastic Agents; Apoptosis; Benzoates; Benzofurans; Cell Adhesion; Cell Line, Tumor; Cell Nucleus Shape; Cell Proliferation; Cell Survival; Drug Discovery; Drug Screening Assays, Antitumor; Emodin; Humans; Hydroxybenzoates; Lichens; Neoplasms; Osmolar Concentration; S Phase

Five compounds representative of major structural classes of lichen polyketides, VIZ. (+)-usnic (1), salazinic (2), vulpinic (3), gyrophoric (4), and evernic acids (5), were investigated for their ability to affect cell proliferation or wound healing, two functional targets of relevance for research on cancer or tissue regeneration. The experiments were carried out on MM98 malignant mesothelioma cells, A431 vulvar carcinoma cells, and HaCaT keratinocytes. The NRU and CV cytotoxicity assays showed high toxicity for (+)-usnic acid, intermediate toxicity for vulpinic acid, and low toxicity for salazinic, gyrophoric and evernic acids. Scratch wounding experiments on HaCaT monolayers, in the presence of subtoxic doses of lichen compounds, showed strong wound closure effects by (+)-usnic and gyrophoric acid, an intermediate effect by vulpinic and salazinic acids, and no effect by evernic acid. A combination of (+)-usnic and gyrophoric acids gave a further increase in the wound closure rates. The results of a cell migration test correlated with the wound healing data. In conclusion, (+)-usnic acid might be a particularly interesting compound for the prevention of hyperproliferation syndromes, while (+)-usnic and gyrophoric acids qualify as interesting leads in the promotion of tissue regeneration.

Topics: Antineoplastic Agents, Phytogenic; Benzoates; Benzofurans; Cell Line, Tumor; Cell Proliferation; Female; Furans; Humans; Hydroxybenzoates; Keratinocytes; Lactones; Lichens; Neoplasms; Phenylacetates; Phytotherapy; Plant Extracts; Salicylates; Wound Healing

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

The sensitivity of the human keratinocyte cell line HaCaT to several lichen metabolites isolated from Parmelia nepalensis and Parmelia tinctorum was evaluated. The tridepside gyrophoric acid (6), the dibenzofuran derivative (+)-usnic acid (1), and the didepside diffractaic acid (5) were potent antiproliferative agents and inhibited cell growth, with IC50 values of 1.7, 2.1, and 2.6 microM, respectively. Methyl beta-orcinolcarboxylate (2), ethyl hematommate (3), the didepside atranorin (4), and (+)-protolichesterinic acid (7) did not influence keratinocyte growth at concentrations of 5 microM. Keratinocytes were further tested for their susceptibility to the action of the potent antiproliferative agents on plasma membrane integrity. The release of lactate dehydrogenase activity into the culture medium was unchanged as compared to controls, documenting that the activity of gyrophoric acid (6), (+)-usnic acid (1), and diffractaic acid (5) was due to cytostatic rather than cytotoxic effects.

Topics: Anisoles; Antineoplastic Agents; Arachidonic Acid; Benzoates; Benzofurans; Cell Division; Humans; Hydroxybenzoates; Keratinocytes; L-Lactate Dehydrogenase; Lichens; Lipoxygenase; Tumor Cells, Cultured