Vulpinic Acids Research Articles

Antiproliferative, antimigratory, and apoptotic effects of diffractaic and vulpinic acids as thioredoxin reductase 1 inhibitors on cervical cancer.

Cervical cancer is among the most frequently observed cancer types in females. New therapeutic targets are needed because of the side impacts of existing cancer drugs and the inadequacy of treatment methods. Thioredoxin reductase 1 (TrxR1) is often overexpressed in many cancer cells, and targeting TrxR1 has become an attractive target for cancer therapy. This study investigated the anticancer impacts of diffractaic and vulpinic acids, lichen secondary metabolites, on the cervical cancer HeLa cell line. XTT findings demonstrated showed that diffractaic and vulpinic acids suppressed the proliferation of HeLa cells in a dose- and time-dependent manner and IC50 values were 22.52μg/ml and 66.53μg/ml at 48h, respectively. Each of these lichen metabolites significantly suppressed migration. Diffractaic acid showed an increase in both the BAX/BCL2 ratio by qPCR analysis and the apoptotic cell population via flow cytometry analysis on HeLa cells. Concerning vulpinic acid, although it decreased the BAX/BCL2 ratio in this cells, it increased apoptotic cells according to the flow cytometry analysis results. Diffractaic and vulpinic acids significantly suppressed TrxR1 enzyme activity rather than the gene and protein expression levels in HeLa cells. This research demonstrated for the first time, that targeting TrxR1 with diffractaic and vulpinic acids was an effective therapeutic strategy for treating cervical cancer.

Neuroprotective activity and cytotoxic potential of two Parmeliaceae lichens: Identification of active compounds

BackgroundLichens are symbiotic organisms capable of producing unique secondary metabolites, whose pharmacological activities are attracting much interest. PurposeThe present study aimed to investigate the in vitro neuroprotective effects and anticancer potential of methanol extracts of two Parmeliaceae lichens: Cetraria islandica and Vulpicida canadensis. The chemical composition of the two lichens was also determined. MethodsNeuroprotective activity was studied with respect to the antioxidant properties of the extracts; radical scavenging tests (ORAC and DPPH assays) were performed and oxidative stress markers (intracellular ROS production, caspase-3 activity, MDA and glutathione levels) were assessed in a hydrogen peroxide-induced oxidative stress model in astrocytes. Cytotoxic activity was tested against human HepG2 (hepatocellular carcinoma) and MCF-7 (breast adenocarcinoma) cell lines. ResultsCell viability studies identified a single concentration for each extract that was subsequently used to measure oxidative stress markers. Lichen extracts were able to reverse the oxidative damage caused by hydrogen peroxide, thus promoting astrocyte survival. Both lichen extracts also had anticancer activity in the cell lines, with IC50 values of 19.51–181.05 µg/ml. The extracts had a high total phenolic content, and the main constituents identified by HPLC were fumarprotocetraric acid in Cetraria islandica, and usnic, pinastric and vulpinic acids in Vulpicida canadensis. The biological activities of the lichen extracts can be attributed to these secondary metabolites. ConclusionThe lichen species studied are promising sources of natural compounds with neuroprotective activity and cytotoxic potential, and warrant further research.

ChemInform Abstract: Synthesis of Vulpinic Acids from Dimethyl Tartrate.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: 3‐Aryltetronic Acids: Efficient Preparation and Use as Precursors for Vulpinic Acids.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis of vulpinic acids from dimethyl tartrate

A series of vulpinic acids differing by the aryl or heteroaryl groups placed in the ester α-position were prepared by Suzuki–Miyaura cross-coupling involving a common iodide and the corresponding aryl boronates. The preparation of the iodide precursor from (+)-dimethyl l-tartrate required four steps: the esterification of one hydroxyl group, a Dieckmann cyclization allowing the construction of the tetronic acid moiety, a dehydration leading to the installation of the exocyclic double bond and lastly, an N-iodosuccinimide-mediated iodation of the alkene obtained.

3-Aryltetronic Acids: Efficient Preparation and Use as Precursors for Vulpinic Acids

3-Aryltetronic acids were prepared in one step by treatment of a mixture of methyl arylacetates and methyl hydroxyacetates with potassium tert-butoxide, via tandem transesterification/Dieckmann condensation. Several mushroom or lichen pigments, vulpinic acids, were synthesized from 3-(4-methoxyphenyl)tetronic acid in three steps involving the reaction of the corresponding dianion with an alpha-ketoester and the dehydration of the tertiary alcohols obtained into mixtures of (E)- and (Z)-alkenes, which were converted under UV irradiation at 254 nm to natural (E)-isomers. Syntheses of pinastric acid, 4,4'-dimethoxyvulpinic acid, and the first synthesis of recently isolated methyl 3',5'-dichloro-4,4'-di-O-methylatromentate were hence achieved in an efficient manner.

Synthesis of vulpinic and pulvinic acids from tetronic acid

A common precursor, tetronic acid, was used in the synthesis of several vulpinic acids and pulvinic acids, which are pigments found in several lichens and mushrooms. The key features of this method are a two-step alkylidenation of benzyl tetronate and a Suzuki–Miyaura cross-coupling. The synthesis of several natural products, vulpinic acid, pinastric acid, xerocomic acid is described.

ChemInform Abstract: Flexible Synthesis of Vulpinic Acids from Tetronic Acid.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Flexible synthesis of vulpinic acids from tetronic acid

Several vulpinic acids were synthesized in a few steps from a single precursor, the tetronic acid. This commercial compound was converted in a few steps to an iodide. Suzuki–Miyaura cross-couplings involving this common intermediate and various arylboronates allowed to gain access to several vulpinic acids (or methyl pulvinates). Among them, two natural products, vulpinic acid and pinastric acid, were prepared.

Functions of Lichen Substances: Deleterious Effects of Usnic and Vulpinic Acids towards the Generalist HerbivoreSpodoptera littoralis

Functions of Lichen Substances: Deleterious Effects of Usnic and Vulpinic Acids towards the Generalist Herbivore<i>Spodoptera littoralis</i>

Vulpinic acids inhibit influenza (RNA) viruses but not herpes (DNA) viruses

Three synthetic vulpinic acids inhibited two influenza RNA viruses, type A (Philippine) and B (Paraha), in tissue culture with ID50 values ranging from 3.9 to 15.5 μg/ml. They had no activity against a third influenza virus or against two herpes viruses.

QUANTITATIVE VARIATION IN VULPINIC AND PINASTRIC ACIDS PRODUCED BY TUCKERMANNOPSIS PINASTRI (LICHEN‐FORMING ASCOMYCOTINA, PARMELIACEAE)

Tuckermannopsis pinastri is a lichen species found commonly on rocks and tree branches in boreal and alpine habitats in the northern United States. Members of this species produce three yellow‐pigmented phenolic compounds: usnic, pinastric, and vulpinic acids. The objective of our study was to quantify the variation in concentration of the latter two of these compounds in relation to substrate factors, chlorophyll content, and thallus size. Using high‐performance liquid chromatography, we analyzed 120 thalli of T. pinastri collected randomly from a single large population located at Spruce Knob, West Virginia. Although individuals were sampled from both tree and rock substrates that differed markedly in light intensity, these environmental factors were not correlated with observed variations in vulpinic or pinastric acid concentrations. Instead, compound concentrations were correlated most closely with thallus size, with small rather than large thalli having the highest concentrations of the two compounds. Small thalli did not have higher concentrations of chlorophylls than large thalli, however, which suggests that the rate of production of secondary compounds by the fungus in T. pinastri is independent of algal biomass. Inasmuch as lichen secondary compounds serve a defensive role against microorganisms and herbivores, our results suggest that small, juvenile thalli are better defended than more mature thalli.

Quantitative Variation in Vulpinic and Pinastric Acids Produced by Tuckermannopsis pinastri (Lichen-Forming Ascomycotina, Parmeliaceae)

Tuckermannopsis pinastri is a lichen species found commonly on rocks and tree branches in boreal and alpine habitats in the northern United States. Members of this species produce three yellow-pigmented phenolic compounds: usnic, pinastric, and vulpinic acids. The objective of our study was to quantify the variation in concentration of the latter two of these compounds in relation to substrate factors, chlorophyll content, and thallus size. Using high-performance liquid chromatography, we analyzed 120 thalli of T. pinastri collected randomly from a single large population located at Spruce Knob, West Virginia. Although individuals were sampled from both tree and rock substrates that differed markedly in light intensity, these environmental factors were not correlated with observed variations in vulpinic or pinastric acid concentrations. Instead, compound concentrations were correlated most closely with thallus size, with small rather than large thalli having the highest concentrations of the two compounds. Small thalli did not have higher concentrations of chlorophylls than large thalli, however, which suggests that the rate of production of secondary compounds by the fungus in T. pinastri is independent of algal biomass. Inasmuch as lichen secondary compounds serve a defensive role against microorganisms and herbivores, our results suggest that small, juvenile thalli are better defended than more mature thalli.

Vulpinic and Pinastric Acids as Lichen Antiherbivore Compounds: Contrary Evidence

The lichen-eating slug Pallifera varia consistently ate discs cut from the thallus of Cetraria pinastri, which produces vulpinic and pinastric acids, and rejected those from the morphologically similar C. oakesiana, which produces fatty acids including caperatic acid. In a second experiment, acetone extracts of the pre- ferred C. pinastri did not deter feeding activity by the slugs but those of the avoided C. oakesiana did. Concentrations of vulpinic and pinastric acids in the thalli of C. pinastri appear to be too low to deter P. varia grazing. Caperatic acid and the other fatty acids ofC. oakesiana appear to be more effective antiherbivore compounds than the vulpinic and pinastric acids of C. pinastri. For nearly 100 years investigators have been suggesting that certain lichen compounds protect slow-growing thalli from predation, although the suggestion has sometimes been hotly debated (reviews: Smith 1921; Gerson & Seaward 1977; Rundel 1978). Two com- pounds most frequently mentioned as defense compounds are the pulvinic acid derivatives vulpinic and pinastric acids. Smith commented (1921) that, although lichen substances appeared from evidence available at that time to be general irritants when consumed, lichens were never poisonous except in two instances: Letharia vulpina, which produces vulpinic acid, and Cetraria pinastri, which produces both vulpinic and pinastric acids. In more recent laboratory studies, vulpinic acid has been shown to elicit significant reductions in the feeding activity of several invertebrate grazers (Slansky 1979; Stephenson & Rundel 1979). Slansky's results, obtained using larvae of the polyphagous insect pest Spodoptera ornithogalli (Guenee), suggested that vulpinic acid functioned as a deterrent rather than a poison; when larvae were forced to consume food treated with vulpinic acid or starve, larval growth was not significantly different from that of control larvae. Even if vulpinic acid is not the potent toxin it was once believed to be, however, it appeared from Slansky's and other studies that vulpinic acid is at least a repellant or an inhibitor compound capable of discouraging generalist herbivore feeding. This paper reports results of feeding-preference studies done using the lichen herbivore Pallifera varia Hubricht, a slug species from western Virginia known to consume lichens (Lawrey 1980). These results suggest that vulpinic acid and the related pulvinic acid de- rivative pinastric acid are not as universally inhibitory to lichen herbivores as they are frequently assumed to be.

Regiospecific synthesis of substituted vulpinic acids

Regiospecific synthesis of substituted vulpinic acids

Vulpinic acids as potential antiinflammatory agents. 1. Vulpinic acids with substituents in the aromatic rings.

The preparation of a series of vulpinic acids, substituted in either or both of the aromatic rings, is described. The compounds were found to be active in the adjuvant arthritis test in rats. High activity combined with an acceptable therapeutic ratio was confined to analogs with electron-withdrawing substituents in the meta positions of the rings.

Application of ozonolysis and gas chromatography for structure elucidation of substituted vulpinic acids

Application of ozonolysis and gas chromatography for structure elucidation of substituted vulpinic acids

A study of the condensation between o-phenylenediamine and pulvinic acid derivatives

The product (IXb) of the condensation at about 200° of o-phenylenediamine with pulvinic acid, vulpinic acid and pulvinic dilactone yields by hydrolytic fission 2-benzylbenziminazole and by ozonolysis 2-benzoylbenziminazole. Vulpinic acid methyl ether also gives IXb as the main product and its N-methyl derivative as minor product, showing that under the basic conditions and high temperature used, demethylation of the enol ether and partial transfer of methyl group to nitrogen occur. Methylation of IXb yields the N-methyl compound; this and its spectral properties show that it is in the keto form. At room temperature, vulpinic and pulvinic acids do not react; however, pulvinic dilactone yields two products: (1) an intermediate amide forming IXb on heating and (2) a product resulting from the condensation of one molecule of diamine with two of the dilactone.