Pulvinic Acid Derivatives Research Articles

Pulvinic Acid Derivative Pigments in Lanmaoa asiatica and L. macrocarpa.

Lanmaoa asiatica G. Wu & Zhu L. Yang and L. macrocarpa N. K. Zeng, H. Chai & S. Jiang are two important gourmet bolete in China, and locally named "Jian Shou Qing" meaning their fruiting bodies turn blue after bruising. The genus represents a distinct lineage in Boletaceae. The pigment(s) associated with the discoloration in Lanmaoa has not been identified. The aim of this study was to determine the pigment(s) underpinning the bluing reaction of L. asiatica and L. macrocarpa when bruised. Potential compounds were isolated by HPLC and identified by LC-HRMS and NMR. In total five to six pigments of hydroxylated pulvinic acid derivatives were detected with similar distribution patterns in both L. asiatica and L. macrocarpa, which by abundance were variegatic acid, variegatorubin, xerocomic acid (and/or isoxerocomic acid), xerocomorubin, and atromentic acid. Variegatic acid, the most abundant pigment, was isolated by HPLC, and the structure was further characterized by NMR. The amount of variegatic acid increased after regular cooking, which may suggest its enhanced health benefit as human diet. The types of pigments that cause bluing reactions often differ among families of Boletales. Our results showed that the pigments in Lanmaoa belong to the category of hydroxylated pulvinic acid derivatives, the major bluing compounds in Boletaceae.

Constituents from the Polar Extract of Pisolithus arhizus and Their Anti-inflammatory Activity.

The phytochemical study of the Pisolithus arhizus fruiting body methanol extract led to the isolation of six new triterpenoids (1-6) and one new naphthalenoid pulvinic acid derivative (7), together with five known compounds, including norbadione A (8). Their structure was established from 1D and 2D NMR spectroscopy and HRESIMS analyses. The absolute configuration of the triterpenoids was determined by circular dichroism. The two pulvinic acid derivatives 7 and 8, showing the highest activity in modulating IL-6 secretion, were tested for their effect on COX-2, STAT3, and p-STAT3 proteins; both compounds were able to downregulate p-STAT3.

IR and UV-VIS spectroscopic characterization of norbadione A and study of the electronic properties of other pigments derived from pulvinic acid

Pulvinic acid-derivative pigments are characterized by the presence of one or more units of pulvinic acid (1) in their molecular structures. Due to their highly conjugated structures, this class of pigments presents significant photochemical properties, including the absorption of UV radiation with high coefficient absorption bands. Here, the spectroscopic characterization of norbadione A (2), a naphtalenoid pulvinic acid derivative isolated from the fungus Pisolithus tinctorius, was made by comparison of its IR and UV-VIS data obtained from experimental and theoretical procedures. Linear correlation between the experimental and theoretical wavenumbers obtained in the IR spectroscopic analyses presented a coefficient of determination (R²) of 0.99576 with a linear equation y = 0.9729x +37.26261, confirming the proposed chemical structure of norbadione A (2). All fundamental vibrational modes were assigned using theoretical quantum calculations. The experimental UV-VIS spectrum of 2 presented bands at 270, 371, and 419 nm, and quantum chemical calculations enabled the assignment of the electronic transitions in each band. Additionally, the electronic properties of pulvinic acid (1) and its derivatives norbadione A (2), badione A (3), bisnorbadioquinone A (4), and pisoquinone (5) were investigated. For all compounds, the Frontier Molecular Orbitals and Fukui functions were calculated at a B3LYP/6-311++G(d,p) computational level in the gas phase. Distinct regions of HOMO and LUMO molecular orbitals were observed, which means that the molecules may have different reactivity; also that the reactivity of the derivative compounds is greater than the precursor acid 1.

Mass Spectrometry Imaging of Specialized Metabolites for Predicting Lichen Fitness and Snail Foraging

Lichens are slow-growing organisms supposed to synthetize specialized metabolites to protect themselves against diverse grazers. As predicted by the optimal defense theory (ODT), lichens are expected to invest specialized metabolites in higher levels in reproductive tissues compared to thallus. We investigated whether Laser Desorption Ionization coupled to Mass Spectrometry Imaging (LDI-MSI) could be a relevant tool for chemical ecology issues such as ODT. In the present study, this method was applied to cross-sections of thalli and reproductive tissues of the lichen Pseudocyphellaria crocata. Spatial mapping revealed phenolic families of metabolites. A quantification of these metabolites was carried out in addition to spatial imaging. By this method, accumulation of specialized metabolites was observed in both reproductive parts (apothecia and soralia) of P. crocata, but their nature depended on the lichen organs: apothecia concentrated norstictic acid, tenuiorin, and pulvinic acid derivatives, whereas soralia mainly contained tenuiorin and pulvinic acid. Stictic acid, tenuiorin and calycin, tested in no-choices feeding experiments, were deterrent for N. hookeri while entire thalli were consumed by the snail. To improve better knowledge in relationships between grazed and grazing organisms, LDI-MSI appears to be a complementary tool in ecological studies

Photoprotective Properties of Natural Pulvinic Acid Derivatives toward Ultraviolet-Induced Damages

Pulvinic acid derivatives are considered as worthy to be evaluated as skin protection factor toward ultraviolet-induced damages because of their colors and locations in lichens. Due to the lack of literature about photo-protective features of pulvinic acid derivatives, their cosmetic potentials for skin protection were evaluated in silico, for the first time. Computational chemistry, biology and pharmacology platforms such as Gaussian, GAMESS, PASS, PaDEL-DDPredictor and VEGA QSAR platforms were employed to determine the activities of pulvinic acid derivatives. Pulvinic acid derivatives were divided into three groups as the most promising, promising and unpromising compounds according to the calculated p-values. Although leprapinic acid, demethylleprapinic acid, pinastric acid, leprapinic acid methyl ether, 4-hydroxyvulpinic acid and vulpinic acid were determined as the most promising compounds, epanorin and rhizocarpic acid were identified as promising compounds. The proposed model seems to be reliable because the calculated p-value for vulpinic acid was found to be compatible with previously obtained experimental results. The pulvinic acid derivatives that were identified as the most promising ones should be therefore further studied by in vitro and in vivo multiple experiments.

Corticolous sorediateLecanoraspecies (Lecanoraceae, Ascomycota) containing atranorin in Europe

AbstractSixteen sorediate epiphytic species ofLecanorawith atranorin from Europe are reported here.Lecanora substerilisis described as a new species from Carpathian beech forests in the Czech Republic, Slovakia, Romania and Ukraine; it belongs to theL.subfuscagroup in its strict sense and is characterized by its usually verrucose thallus, sorediate apothecial margin, epihymenium with coarse granules at paraphyses tips, amphithecium with large crystals and it produces atranorin and fatty acid(s). A new, yellow chemotype ofL. barkmanianacontaining pulvinic acid derivatives is recognized from Austria. Morphological, ecological and chemical variation inL. exspersa, L. farinariaandL.variolascensis discussed in detail, and brief comments on the remaining 11 species are provided. Evaluation of the type material and molecular data indicate that the predominantly saxicolousL. caesiosorais a sorediate form ofL. cenisia. Molecular data confirmed the identities of the sorediate forms ofL. albellaandL. allophanathat are conspecific with their fertile counterparts. New Central European localities are listed for the rare species,L. barkmaniana,L. exspersa,L. mughosphagneti,L. norvegicaandL. variolascens. Positions in ITS and mtSSU phylogenies are outlined for most species. Identification keys to fertile as well as sterile populations are provided.

Henfellra muriformisgen. et sp. nov., a New Dictyosporous Pycnidial Fungus onCandelariella, with a Key to the Lichenicolous Fungi Known from that Genus

Hawksworth, D. L., Halıcı, M. G., Kocakaya, Z. & Kocakaya, M. 2016. Henfellra muriformis gen. et sp. nov., a new dictyosporous pycnidial fungus on Candelariella, with a key to the lichenicolous fungi known from that genus. — Herzogia 29: 329–336.The new generic name Henfellra gen. nov. is introduced for a new species of pycnidial fungus with hyaline muriform euseptate conidia, H. muriformis sp. nov., discovered on Candelariella antennaria in Turkey. This is the first lichenicolous fungus with muriform conidia to be recognized, and the separation from non-lichenicolous pycnidial genera with muriform conidia, such as Camarosporium, is discussed. A key to the 16 lichenicolous fungi now known to occur on Candelariella species worldwide is provided, and it is noted that the generic placement of several of those will need to be reassessed as they do not appear to be congeneric with the type species of the genera in which they are currently placed. Interestingly, several rather widespread lichenicolous genera have yet to be encountered on the genus, and few are known from the three other genera of Candelariellaceae; whether this is attributable to antifungal properties of the pulvinic acid derivatives they contain merits exploration.

ChemInform Abstract: Synthesis of Secondary Metabolites from Higher Fungi

AbstractReview: [160 refs.

In Silico Discovery of Novel Potent Antioxidants on the Basis of Pulvinic Acid and Coumarine Derivatives and Their Experimental Evaluation.

A pigment from the edible mushroom Xerocomus badius norbadione A, which is a natural derivative of pulvinic acid, was found to possess antioxidant properties. Since the pulvinic acid represents a novel antioxidant scaffold, several other derivatives were recently synthetized and evaluated experimentally, along with some structurally related coumarine derivatives. The obtained data formed the basis for the construction of several quantitative structure-activity and pharmacophore models, which were employed in the virtual screening experiments of compound libraries and for the prediction of their antioxidant activity, with the goal of discovering novel compounds possessing antioxidant properties. A final prioritization list of 21 novel compounds alongside 8 established antioxidant compounds was created for their experimental evaluation, consisting of the DPPH assay, 2-deoxyribose assay, β-carotene bleaching assay and the cellular antioxidant activity assay. Ten novel compounds from the tetronic acid and barbituric acid chemical classes displayed promising antioxidant activity in at least one of the used assays, that is comparable to or even better than some standard antioxidants. Compounds 5, 7 and 9 displayed good activity in all the assays, and were furthermore effective preventers of oxidative stress in human peripheral blood mononuclear cells, which are promising features for the potential therapeutic use of such compounds.

Synthesis of Secondary Metabolites from Higher Fungi

Higher fungi are a promising source of new bioactive natural products with great structural diversity, ranging from polyketides to terpenoids and alkaloids. Many of these structures are a challenge for synthetic organic chemists who have been inspired to develop new total syntheses. Nevertheless, reviews covering syntheses of fungal natural products are lacking. One aim of this review is to close this gap and to present a selection of more recent syntheses of fungal secondary metabolites from different structural classes. Secondly, this review intends to demonstrate that there are many more motivations for the synthesis of natural products than to confirm a proposed structure or to report the first total synthesis of a new natural product. Thirdly, this review is intended to stimulate the interest of organic chemists in the synthesis of fungal natural products. 1 History and Importance of (Fungal) Secondary Metabolites 2 Reasons for the Synthesis of Fungal Natural Products 3 Total Syntheses of Selected Fungal Natural Products 3.1 Terpenes 3.1.1 Sesquiterpenes 3.1.1.1 Polyquinanes 3.1.1.2 Drimanes 3.1.2 Diterpenes: Cyathanes 3.1.3 Terpenes Containing a Butenolide Moiety 3.2 Alkaloids 3.3 Natural Products Derived from the Shikimate Pathway 3.3.1 Pulvinic Acid Derivatives and Terphenyl Quinones 3.3.2 Shikimate Pathway Derived Macrolides 3.3.3 Strobilurins 3.4 Aromatic Polyketides 3.4.1 Quinones 3.4.2 Resorcylates and Catechols 3.5 Sugar Derivatives 4 Conclusion and Outlook

FT-Raman spectroscopy of the Candelaria and Pyxine lichen species: A new molecular structural study

In this work the chemistry of the lichens Candelaria fibrosa and Pyxine coccifera have been investigated for the first time using FT-Raman spectroscopy with the help of quantum mechanical DFT calculations to support spectral band assignments. The non-destructive spectral vibrational analysis provided evidence for the presence of pulvinic acid derivatives and conjugated polyenes, which probably belong to a carotenoid with characteristic signatures at ca. 1003, 1158 and 1525 cm−1 assigned respectively to δ(C–CH3), ν(C–C) and ν(CC) modes. The identification of features arising from chiodectonic acid in the Pyxine species and calycin and pulvinic dilactone pigments in C. fibrosa were assisted by the quantum mechanical DFT calculations. Raman spectroscopy can provide important spectroscopic data for the identification of the biomarker spectral signatures nondestructively for these lichen pigments without the need for chemical extraction processes.

Development of models for prediction of the antioxidant activity of derivatives of natural compounds

Antioxidants are important for maintaining the appropriate balance between oxidizing and reducing species in the body and thus preventing oxidative stress. Many natural compounds are being screened for their possible antioxidant activity. It was found that a mushroom pigment Norbadione A, which is a pulvinic acid derivative, shows an antioxidant activity; the same was found for other pulvinic acid derivatives and structurally related coumarines. Based on the results of in vitro studies performed on these compounds as a part of this study quantitative structure–activity relationship (QSAR) predictive models were constructed using multiple linear regression, counter-propagation artificial neural networks and support vector regression (SVR). The models have been developed in accordance with current QSAR guidelines, including the assessment of the models applicability domains. A new approach for the graphical evaluation of the applicability domain for SVR models is suggested. The developed models show sufficient predictive abilities for the screening of virtual libraries for new potential antioxidants.

Parmeliaceae family: phytochemistry, pharmacological potential and phylogenetic features

Parmeliaceae is the largest family of lichenized fungi comprising about 2700 species distributed in about 80 genera. A wide array of secondary metabolites including depsides, depsidones, aliphatic acids, triterpenes, anthraquinones, secalonic acids, pulvinic acid derivatives and xanthones have been identified within this family. Many of these bioactive compounds such as usnic acid and atranorin are exclusively found in this family, being of great relevance for the systematics and phylogeny. Moreover, these compounds exert different biological roles including antimicrobial, antioxidant, cytotoxic, anti-inflammatory, analgesic and enzyme inhibitory actions. The current review focuses on the phytochemistry and main phylogenetic aspects of Parmeliaceae, and it discusses the pharmacological findings and mechanisms of action of their extracts and isolated compounds. The present work actually collects information related to more than 65 lichen species (from 21 different genuses and heterogeneous distribution) and 75 isolated metabolites. As reported, the best studied genus from a pharmacological point of view is Parmelia, followed by Usnea. At the species level, Cetraria islandica and Evernia prunastri attract remarkable interest in their bioactive activities and metabolite content. The major pharmacological activities investigated on extracts and compounds from Parmeliaceae spp. have been antimicrobial, anticancer and antioxidant potentials; and regarding isolated compounds, the aforementioned usnic acid and atranorin are among the most studied metabolites. Reviewed data suggest that some of these lichens and natural compounds are worthy of further investigation.

ChemInform Abstract: New Pulvinic Acid and Phenylalaninol Derivatives from the Mushrooms Retiboletus griseus and R. nigerrimus.

ChemInform Abstract: New Pulvinic Acid and Phenylalaninol Derivatives from the Mushrooms Retiboletus griseus and R. nigerrimus.

New Pulvinic Acid and Phenylalaninol Derivatives from the Mushrooms Retiboletus griseus and R. nigerrimus

Abstract The close genetic relationship of the mushrooms Retiboletus griseus and R. nigerrimus is supported by the occurrence of the orange-yellow retiboletic acid, resp. its methyl ester, in both species. The structures of these highly substituted pulvinic acid derivatives have been elucidated by spectroscopic investigations. R. nigerrimus also contains two N-protocatechuyl-L-phenylalaninol derivatives, nigerrimin A and B, the first reported occurrence of such compounds in nature. Their configuration was established by the synthesis of nigerrimin B

UV-protectant metabolites from lichens and their symbiotic partners

Lichens are structurally complex symbiotic organisms that are exposed to a wide variety of external conditions (extreme temperatures, desiccation, UV radiation, etc.). These poikilohydric organisms have developed various mechanisms of photoprotection, such as light scattering, radiation screening, thermal dissipation, activation of antioxidant defense and macromolecules and membrane repair. These unique organisms produce a vast array of compounds, with more than 1000 secondary metabolites known. An important protective mechanism of lichens is the production of UV screening compounds, such as phenolic compounds (depsidones, depsides, diphenyl ethers), anthraquinones, xanthones or shikimic acid derivatives (calycin, mycosporines, scytonemin). Due to the harmful effects of the UVA wavelengths of sunlight, the search for new sunscreens remains important. We herein propose a review that focuses on the UV protectants from lichens and their symbiotic partners (lichenized fungi, green alga, cyanobacteria). In fact, lichens produce unique and/or efficient UV filters such as depsidones (lobaric acid, pannarin, etc.), depsides (atranorin, gyrophoric acid, etc.), diphenyl ethers (epiphorellic acids, buellin), bisxanthones (secalonic acids, etc.), mycosporines and MAAs, scytonemin along with classical pigments (melanin, carotenoids). We propose to classify these compounds with regard to their chemical structures and review the physicochemical properties that act as UV filters. While the most abundant lichen polyfunctionalized aromatic compounds, belonging to orsellinic derivatives, are UVB screens, these organisms produce strong UVA filters, e.g., calycin (pulvinic acid derivatives), bisxanthones (secalonic acids), scytonemin or mycosporines and MAAs with the latter ones exhibiting attractive properties as photoprotectants.

USNIC ACID CONTENT AND ANTIOXIDANT ACTIVITY OF THREE LICHEN EXTRACTS

s. PHYTOPHARM 2012 M 68 Obzory po kliniceskoj farmacologii i lekarstvennoj terapii [Reviews of clinical pharmacology and drug therapy] ТОМ 10/2012/2 (+)-USNIC ACID CONTENT AND ANTIOXIDANT ACTIVITY OF THREE LICHEN EXTRACTS © Koptina A. , Shcherbakova A. , Soldati F. , Gabdullin M. , Kanarskiy A. , Ulrich-Merzenich G. 3 Mari State Technical University, Yoshkar-ola, Russia Pharmaton SA, 6934 Bioggio, Switzerland Medical Clinic III, University of Bonn, Willhelmstr. 35–37, 53111 Bonn, Germany lichens produce a variety of secondary metabolites which belong to the depsides, depsidones, dibenzofurans and pulvinic acid derivative family. They proved to be a good source of natural antioxidants (1). Usnic acid uniquely found in many lichens has been reported to have analgesic, antimicrobial, anti-inflammatory, antiplatelet/antithrombotic, antiviral, cytotoxic/antiproliferative, gastroprotective, weight loss, and wound healing activity (2). We examined the (+)-usnic acid content and the anti-oxidative properties of the chloroform extract of lichen: Cladonia sylvatica (l.) hoffm., Evernia prunastri (l.) Ach. and Usnea barbata (l.) Wigg. (s. i.) were collected in Mari El Republic of Russian federation in June, 2011. Reverse phase hPlC analysis was carried out (Perkin Elmer Series 200 hPlC instrument; C18 column (C18; 25 cm ×4.6 mm, 5μm); UV/Vid detector; solvent: methanol-water-phosphoric acid (80:20:.9, v/v/v)). The sample injection volume was 20 μl and the flow rate 1.0 ml/min. A standard of (+)-usnic acid was used. The total antioxidant activity of the extracts was evaluated by the phosphomolybdenum method as described Manojlovic et al. (3). The chloroform extracts of C. sylvatica, E. prunastri and U. barbata showed contents of (+)-usnic acid of 8.91 ± 1.18, 5.68 ± 0.47 and 74.49 ± 8.64 % respectively. The antioxidant activities were: 277.1 ± 20.0, 171.1 ± 17.1 and 205.8 ± 7.2 mg of ascorbic acid (AA) per g of extract respectively; in comparison, the antioxidant activity of the (+)-usnic acid standard was determined as 154 ± 6.5 mg AA/g. We can report that U. barbata is a good source of (+)-usnic acid. Other secondary metabolites than (+)-usnic acid present in C. sylvatica and E. prunastri contribute to their high antioxidant activity and need to be further investigated.

Assessment of Lichens' Metabolic and Degradation Products at Dornava Manor

Five major types of lichen were discovered in the investigated specimens from Dornava Manor. All these lichens and/or their combinations are considered common lichenous overgrowth for the region and its climate. For all of the positively identified lichen species, it is common that they are found on a wide variety of calciferous or base-rich substrata, incl. mortar, brick, roofing tiles, walls, also in large urban areas (are not particularly disturbed by pollution/eutrophication), therefore preferring neutral to basic environment. They are well adapted to sunlight (from scarce direct solar irradiation to sites with very high direct solar irradiation) and can tolerate low water accessibility. In some of the lichens parietin, an orange organic pigment, was found, indicating the sun exposed areas. Additionally, carotenoids and pulvinic acid derivatives were identified, from which the metabolic pathway of lichens can be determined. These products can also represent biomarkers that can be linked to the survival strategies of lichen communities in stressed environmental habitats. For many of the investigated samples the lichens' degradation products like oxalates were identified, mainly calcium oxalate Weddellite, while the ammonium oxalate Oxammite is also possible.

Design and Synthesis of New Antioxidants Predicted by the Model Developed on a Set of Pulvinic Acid Derivatives

Antioxidative activity expressed as protection of thymidine has been investigated for a set of 30 pulvinic acid derivatives. A combination of in vitro testing and in silico modeling was used for synthesis of new potential antioxidants. Experimental data obtained from a primary screening test based on oxidation under Fenton conditions and by an UV exposure followed by back-titration of the amount of thymidine remaining intact have been used to develop a computer model for prediction of antioxidant activity. Structural descriptors of 30 compounds tested for their thymidine protection activity were calculated in order to define the structure-property relationship and to construct predictive models. Due to the potential nonlinearity, the counter-propagation artificial neural networks were assessed for modeling of the antioxidant activity of these compounds. The optimized model was challenged with 80 new molecules not present in the initial training set. The compounds with the highest predicted antioxidant activity were considered for synthesis. Among the predicted structures, some coumarine derivatives appeared to be especially interesting. One of them was synthesized and tested on in vitro assays and showed some antioxidant and radioprotective activities, which turned out as a promising lead toward more potent antioxidants.

Synthesis and Radioprotective Properties of Pulvinic Acid Derivatives

A high-throughput screening method has highlighted the marked antioxidant activity of some pulvinic acid derivatives (PADs) towards oxidation of thymidine, under γ and UV irradiation, and Fenton-like conditions. Here, we report the synthesis of a series of new hydrophilic PADs and the evaluation of their radioprotective efficacy in cell culture. Using a cell-based fluorescent assay, we show that some of these compounds have a pronounced ability to prevent cell death caused by radiation and to allow the subsequent resumption of proliferation. Thus, PADs may be considered as a novel class of radioprotective agents.