No Evidence Was Found for the Presence of Terreolides, Terreumols or Saponaceolides H-S in the Fruiting Bodies of Tricholoma terreum (Basidiomycota, Agaricales).

Two different collections of the gilled wild fungus Tricholoma terreum, collected in Italy, were subjected to phytochemical analysis. The fungal material was confidently identified by analysis of the ITS genomic sequences. Using both HR-LC-MS and NMR techniques, no evidence was found for the presence in the fruiting bodies of terreolides, terreumols or saponaceolides H-S, in striking contrast with the isolation of these terpenoids by Chinese authors from a mushroom collected in France and identified as T. terreum. The main cytotoxic terpenoid identified and isolated from the extracts of the specimens investigated in this work was the C30 derivative saponaceolide B, which had been previously isolated from T. saponaceum and other T. terreum collections. Although saponaceolide B is a rather labile molecule, easily degradable by heat or in acidic conditions, our study indicated that none of the extraction protocols used produced saponaceolide H-S or terreolide/terreumol derivatives, thus excluding the possibility that the latter compounds could be extraction artifacts. Considered together, these findings point to the need for the unambiguous identification of mushroom species belonging to the complex genus Tricholoma, characterized by high variability in the composition of metabolites. Moreover, based on our data, T. terreum must be considered an edible mushroom.

A New Glucosyl Flavone with Inhibitory Activity of Cancer Cell Viability and Other Bioactive Constituents from the Traditional Kurdish Plant Plantago loeflingii L.

A new glucosyl flavone, 5,7,2',5'-tetrahydroxyflavone 7-O-ß-d-glucopyranoside, named loeflingiin, together with apigenin 6-C-glucoside (isovitexin), coumarins citropten and isompinellin, triterpenoids betulin and betulinic acid, and a mixture of phytosterols ß-sitosterol, stigmasterol and campesterol were isolated for the first time from the leaves of wild Plantago loeflingii L. (Plantaginaceae) collected in the Iraqi Kurdistan region. The plant is used by local people to treat wounds and as a vulnerary remedy. The structures of isolated compounds were determined by spectroscopic analysis. The activities of isovitexin and loeflingiinon the viability of breast (MCF7), ovarian (BG-1), endometrial (Ishikawa), and mesothelioma (IST-MES1) human cancer cells and two normal cell lines were determined with an MTT assay. Notably, the new 7-O-glucosyl flavone showed effects higher than cisplatin against the Ishikawa and IST-MESI cell lines. The significant biological activities exhibited by all the compounds isolated from P. loeflingii provided scientific evidence to support the use of the plant in the Kurdish traditional medicine.

New Tricholidic Acid Triterpenoids from the Mushroom Tricholoma ustaloides Collected in an Italian Beech Wood.

The secondary metabolites produced by Tricholoma ustaloides Romagn., a mushroom species belonging to the large Tricholoma genus (Basidiomycota, Tricholomataceae), are unknown. Therefore, encouraged by the interesting results obtained in our previous chemical analyses of a few Tricholoma species collected in Italian woods, we aimed to investigate the secondary metabolites of Tricholoma ustaloides. The chemical analysis involved the isolation and characterization of secondary metabolites through an extensive chromatographic study. The structures of isolated metabolites, including the absolute configuration, were established based on a detailed analysis of MS, NMR spectroscopic, optical rotation, and circular dicroism data, and on comparison with those of related compounds reported in the literature. Two novel lanostane triterpenoids, named tricholidic acids B and C, together with triglycerides, a mixture of free fatty acids, five unidentified metabolites, and the known rare saponaceolides F and J, tricholidic acid, and tricholomenyn C, were isolated from an EtOAc extract of fruiting bodies of Tricholoma ustaloides that were collected in an Italian beech wood. This is the second example of isolation of tricholidic acid derivatives from a natural source. Saponaceolides F and J exhibited high cytotoxicity (IC50 values ≤ 10 µM) against a panel of five human cancer cell lines. The toxicity against myeloid leukemia (HL-60), lung cancer (A-549), hepatocellular cancer (HepG2), renal cancer (Caki-1), and breast cancer (MCF-7) cells was higher than that shown by the very well-known cytotoxic drug cisplatin.

New Tricholomalides D-G from the Mushroom Tricholoma ustaloides Grown in an Italian Beech Wood.

Four novel seconeodolastane diterpenoids, named tricholomalides D-G, were isolated, together with the known tricholomalide C, from the fruiting bodies of Tricholoma ustaloides Romagn., a species belonging to the large Tricholoma genus of higher mushrooms (Basidiomycota, family Tricholomataceae). They were isolated through multiple chromatographic separations, and the structures, including the absolute configuration, were established through a detailed analysis of MS, NMR, and CD spectral data and comparison with related compounds reported in the literature, which has been thoroughly revised.

A Validated HPLC-UV-ESI-IT-MS Method for the Quantification of Carnosol in Lepechinia mutica, a Medicinal Plant Endemic to Ecuador.

The diphenolic diterpene carnosol was isolated from several species of the family Lamiaceae, including Lepechinia mutica, a medicinal plant endemic to Ecuador. The compound has exhibited high antioxidant, anti-inflammatory, antimicrobial, neuroprotective, and antifungal properties, as well as promising cytotoxicity against prostate, breast, skin, leukemia, and human colon cancer cell lines. In this paper, we developed and validated a simple, accurate, and reliable analytical HPLC-UV-ESI-IT-MS method, carried out on a C18 column, which is potentially suitable to quantify carnosol in plant extracts. The procedure complied with the established ICH validation parameters of analytical range (linearity in the range of 0.19-5.64 µg/g dried leaves; REAVERGE = 4.9%; R2 = 0.99907), analysis repeatability (RSD = 2.8-3.6%), intermediate precision (RSD = 1.9-3.6%), accuracy (estimated as % carnosol recovery in the range of 81 to 108%), and robustness. Finally, the LOD (0.04 µg/mg) and LOQ (0.19 µg/mg) values of carnosol/dried leaves were determined. Using this validated method, the content of carnosol in L. mutica was estimated to be 0.81 ± 0.04 mg/g of dried leaves (0.081%).

Chemical Characterization and Biological Activity of the Essential Oil from Araucaria brasiliensis Collected in Ecuador.

The purpose of this study was to determine the chemical composition, physical properties, enantiomeric composition and cholinesterase inhibitory activity of the essential oil (EO) steam-distilled from the leaves of the plant Araucaria brasiliensis Loud. collected in Ecuador. The chemical composition was determined by gas chromatography coupled to mass spectrometry (GC-MS) analysis on two capillary GC columns (DB5-ms and HP-INNOWax). Thirty-three compounds were identified in the EO; the main compounds were beyerene (26.08%), kaurene (24.86%), myrcene (11.02%), α-pinene (9.99%) and 5,15-rosadiene (5.87%). Diterpene hydrocarbons (65.41%), followed by monoterpene hydrocarbons (21.11%), were the most representative components of the EO. Enantioselective analysis of the EO showed four pairs of enantiomeric compounds, α-pinene, camphene, γ-muurolene and δ-cadinene. In an in vitro assay, the EO showed moderate inhibitory activity towards the enzyme butyrylcholinesterase (BuChE) (95.7 µg/mL), while it was inactive towards acetylcholinesterase (AChE) (225.3 µg/mL). Further in vivo studies are needed to confirm the anticholinesterase potential of the EO.

Bio-Active Compounds from Teucrium Plants Used in the Traditional Medicine of Kurdistan Region, Iraq.

Herbal medicine is still widely practiced in the Kurdistan Region, Iraq, especially by people living in villages in mountainous regions. Seven taxa belonging to the genus Teucrium (family Lamiaceae) are commonly employed in the Kurdish traditional medicine, especially to treat jaundice, stomachache and abdominal problems. We report, in this paper, a comprehensive account about the chemical structures and bioactivities of most representative specialized metabolites isolated from these plants. These findings indicate that Teucrium plants used in the folk medicine of Iraqi Kurdistan are natural sources of specialized metabolites that are potentially beneficial to human health.

Iridoids Isolation from a Phytochemical Study of the Medicinal Plant Teucrium parviflorum Collected in Iraqi Kurdistan.

Herbal medicines are still widely practiced in Kurdistan Region-Iraq, especially by people living in villages on mountainous regions. Among plants belonging to the genus Teucrium (family Lamiaceae), which are commonly employed in the Kurdish traditional medicine, we have analyzed, for the first time, the methanol and aqueous methanol extracts of T. parviflorum aerial parts. The plant is mainly used by Kurds to treat jaundice, liver disorders and stomachache. We aimed to determine the phytochemical profile of the extracts and the structures of the main components, so to provide a scientific rationale for the ancient use of the plant in the ethno-pharmacological field. TLC analysis of the two extracts on silica gel and reversed phase TLC plates, using different visualization systems, indicated similar contents and the presence of phenolics, flavonoids, terpenoids and sugars. The chlorophyll-free extracts exhibited weak/no antimicrobial activities against a panel of bacteria (MICs = 800-1600 µg/mL) and fungal strains (MICs ≥ 5 mg/mL). At the concentration of 600 µg/mL, the methanol extract showed moderate antiproliferative effects against A549 and MCF-7 cancer cell lines in the MTS assay. Moreover, both extracts exhibited a significant dose-dependent free radical scavenging action against the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical (EC50 = 62.11 and 44.25 µg/mL, respectively). In a phytochemical study, a high phenolic content (77.08 and 81.47 mg GAE/g dry extract, respectively) was found in both extracts by the Folin-Ciocalteu assay. Medium pressure liquid chromatographic (MPLC) separation of the methanol extract on a reversed phase cartridge eluted with a gradient of MeOH in H2O, afforded two bioactive iridoid glucosides, harpagide (1) and 8-O-acetylharpagide (2). The structures of 1 and 2 were established by spectral data, chemical reactions, and comparison with the literature. Interestingly, significant amounts of hepatotoxic furano neo-clerodane diterpenoids, commonly occurring in Teucrium species, were not detected in the extract. The wide range of biological activities reported in the literature for compounds 1 and 2 and the significant antiradical effects of the extracts give scientific support to the traditional use in Iraqi Kurdistan of T. parviflorum aerial parts for the preparation of herbal remedies.

Synthesis and antibacterial evaluation of new monobactams.

Monobactams play an important role in antibiotic drug discovery. Based on the structural characteristics of aztreonam and its biological targets, six new monobactam derivatives (2a-c and 3a-c) were synthesized and their in vitro antibacterial activities were investigated. Compounds 2a-c showed higher activities against tested gram-negative bacteria than that of parent aztreonam. Monobactam 2c exhibited the most potent activities, with MIC ranging from 0.25 to 2 µg/mL against most bacteria.

Constituents of Aegle marmelos from Myanmar.

Five compounds (1-5), including three coumarins (1-3) and two alkaloids (4,5) were isolated during the first investigation of the stem bark of Aegle marmelos (L.) Corrêa. collected in Myanmar. Their structures were determined by NMR spectra analysis. Among them, 7´-O-ethylmarmin (1) and 2-O-ethyltembamide (5) were identified as new compounds. Skimmianine (4) showed moderate cytotoxicity against a HeLa cell line, and 7´-O-ethylmarmin (1), marmin (2), and (+)-epoxyaurapten (3) displayed weak radical scavenging activity according to a DPPH scavenging assay.

Phytochemistry and Biological Activities of Iris Species Growing in Iraqi Kurdistan and Phenolic Constituents of the Traditional Plant Iris postii.

A dozen Iris species (Iridaceae) are considered traditional remedies in Kurdistan, especially for treating inflammations. Phytochemical studies are still scarce. The information reported in the literature about Iris species growing in Kurdistan has been summarized in the first part of this paper, although, except for Iris persica, investigations have been performed on vegetal samples collected in countries different from Kurdistan. In the second part of the work, we have investigated, for the first time, the contents of the methanolic extracts of Iris postii aerial parts and rhizomes that were collected in Kurdistan. Both extracts exhibited a significant dose-dependent free radical scavenging and total antioxidant activities, comparable to those of ascorbic acid. Medium-pressure liquid chromatographic separations of the two extracts afforded l-tryptophan, androsin, isovitexin, swertisin, and 2″-O-α-l-rhamnopyranosyl swertisin from the aerial parts, whereas ε-viniferin, trans-resveratrol 3,4'-O-di-ß-d-glucopyranoside, and isotectorigenin were isolated from the rhizomes. This is the first finding of the last three metabolites from an Iris species. The various remarkable biological activities of isolated compounds scientifically sustain the traditional use of I. postii as a medicinal plant.

Structures and Bioactivities of Steroidal Saponins Isolated from the Genera Dracaena and Sansevieria.

The species Dracaena and Sansevieria, that are well-known for different uses in traditional medicines and as indoor ornamental plants with air purifying property, are rich sources of bioactive secondary metabolites. In fact, a wide variety of phytochemical constituents have been isolated so far from about seventeen species. This paper has reviewed the literature of about 180 steroidal saponins, isolated from Dracaena and Sansevieria species, as a basis for further studies. Saponins are among the most characteristic metabolites isolated from the two genera. They show a great variety in structural motifs and a wide range of biological activities, including anti-inflammatory, anti-microbial, anti-proliferative effects and, in most case, remarkable cytotoxic properties.

Components of Volatile Fractions from Eucalyptus camaldulensis Leaves from Iraqi-Kurdistan and Their Potent Spasmolytic Effects.

Inhalation of vapors from a hot tea of Eucalyptus camaldulensis Dehnh. leaves is considered by Iraqi-Kurdistan people an effective spasmolytic and antipyretic remedy for the treatment of respiratory diseases. The constituents of volatile fractions isolated by hydrodistillation from dried leaves of the plant collected in Kurdistan were determined by GC-FID and GC-MS analyses. More than 90% components were identified. The most abundant constituents were 1,8-cineole, p-cymene, α-pinene, terpinen-4-ol, aromadendrene, and α-terpineol. The different volatile fractions induced relaxation on rat isolated aortic and tracheal rings in concentration-dependent manner. These effects appeared to be due to a complex interaction between various terpenoid components rather than being only due to the main oil constituent, 1,8-cineole. The KCa channel and the NO pathway were not significantly involved in the relaxation mechanism, while Ca2+ channels played a major role in the spasmolytic effects.

Bioactive Phytochemical Constituents of Wild Edible Mushrooms from Southeast Asia.

Mushrooms have a long history of uses for their medicinal and nutritional properties. They have been consumed by people for thousands of years. Edible mushrooms are collected in the wild or cultivated worldwide. Recently, mushroom extracts and their secondary metabolites have acquired considerable attention due to their biological effects, which include antioxidant, antimicrobial, anti-cancer, anti-inflammatory, anti-obesity, and immunomodulatory activities. Thus, in addition to phytochemists, nutritionists and consumers are now deeply interested in the phytochemical constituents of mushrooms, which provide beneficial effects to humans in terms of health promotion and reduction of disease-related risks. In recent years, scientific reports on the nutritional, phytochemical and pharmacological properties of mushroom have been overwhelming. However, the bioactive compounds and biological properties of wild edible mushrooms growing in Southeast Asian countries have been rarely described. In this review, the bioactive compounds isolated from 25 selected wild edible mushrooms growing in Southeast Asia have been reviewed, together with their biological activities. Phytoconstituents with antioxidant and antimicrobial activities have been highlighted. Several evidences indicate that mushrooms are good sources for natural antioxidants and antimicrobial agents.

Flavonoids and Stilbenoids of the Genera Dracaena and Sansevieria: Structures and Bioactivities.

The genera Dracaena and Sansevieria (Asparagaceae, Nolinoideae) are still poorly resolved phylogenetically. Plants of these genera are commonly distributed in Africa, China, Southeast Asia, and America. Most of them are cultivated for ornamental and medicinal purposes and are used in various traditional medicines due to the wide range of ethnopharmacological properties. Extensive in vivo and in vitro tests have been carried out to prove the ethnopharmacological claims and other bioactivities. These investigations have been accompanied by the isolation and identification of hundreds of phytochemical constituents. The most characteristic metabolites are steroids, flavonoids, stilbenes, and saponins; many of them exhibit potent analgesic, anti-inflammatory, antimicrobial, antioxidant, antiproliferative, and cytotoxic activities. This review highlights the structures and bioactivities of flavonoids and stilbenoids isolated from Dracaena and Sansevieria.

Phytochemical Investigation of Male and Female Hedyosmum scabrum (Ruiz & Pav.) Solms Leaves from Ecuador.

This article reports the chemical composition of the essential oils obtained by hydrodistillation of male and female H. scabrum fresh leaves. The essential oils, HSMO and HSFO, respectively, were analyzed by GC/MS and GC-FID. A total of 93 components were detected, accounting for 94.8% and 95.3% of HSMO and HSFO, respectively. The prevalent constituents of HSMO were pinocarvone (13.1%), d-germacren-4-ol (12.6%), 1,8-cineole (10.8%), α-pinene (6.4%), and ß-pinene (4.8%), whereas the major components of HSFO were 1,8-cineole (20.5%), linalool (16.5%), α-pinene (15.0%), ß-pinene (6.4%), and sabinene (6.3%). The different enantiomeric distribution of ß-pinene, sabinene, limonene, linalool in the two oils, was determined. The non-volatile esters of p-coumaric and ferulic acids with borneol (1 and 4), cis-chrysanthenol (2 and 5), and cis-pinocarveol (3 and 6) were identified in the leaves after basic hydrolysis and analysis of the NMR spectra of the free acids, and GC/MS spectra of the monoterpene alcohols, respectively. Compounds 2, 3, 5, and 6 have been found in nature for the first time. These findings demonstrated that, from a chemical point of view, male and female individuals of H. scabrum collected in Ecuador seem quite differentiated between each other and from samples of the same species growing in Bolivia and in Peru.

Two New Ergosterol Derivatives from the Basidiomycete Cortinarius glaucopus.

Two new sterols 1 and 2 and five known ones 3 - 7 were isolated for the first time from the fruiting bodies of Cortinarius glaucopus. Their structures were established by 1- and 2D-NMR spectra and HR-FABS-MS. The relative configuration of 1 was firmly determined by comparison of the observed 1 H-1 H couplings and NOESY correlations, with those predicted for the computed geometries of the conformers. Calculations were performed by means of DFT with the B3LYP functional at 6-31 + G(d,p) level of theory, in CHCl3 as the solvent. The structures of the new ergosterol derivatives, called glaucoposterol A (1) and B (2), were thus established as (3S,5R,7R,10R,13R,17R,20S,22R,23R,24R)-5,6-epoxy-3,7,23-trihydroxystrophast-8-en-14-one and (22E,3S,5S,9S,10R,13R,17R,20R,24R)-3,5-dihydroxyergosta-6,8(14),22-trien-15-one, respectively. Moreover, the configuration of known strophasterol C (3) was determined as (3S,5R,6S,7R,10R,13R,17R,20S,22S,24R). Glaucoposterol A (1) and strophasterol C (3) represent the second finding in nature of steroids with the rare strophastane skeleton.

A New Iridoid Dimer and Other Constituents from the Traditional Kurdish Plant Pterocephalus nestorianus Nábelek.

Accompanied by other rare compounds, a new iridoid dimer, named kurdnestorianoside (1), showing an unprecedented secologanol configuration, has been isolated for the first time from the Kurdish medicinal plant Pterocephalus nestorianus, which is used in Kurdistan for treating oral diseases and inflammation. The structure of 1 was established from 1D- and 2D-NMR spectroscopic data. Kaempferol 3-O-[3,6-di-O-(E)-p-coumaroyl]-ß-d-glucopyranoside (7) showed a remarkable antiproliferative activity against several human tumor cell lines.

Chemical Composition, Enantiomeric Analysis, AEDA Sensorial Evaluation and Antifungal Activity of the Essential Oil from the Ecuadorian Plant Lepechinia mutica Benth (Lamiaceae).

This study describes the GC-FID, GC/MS, GC-O, and enantioselective GC analysis of the essential oil hydrodistilled from leaves of Lepechinica mutica (Lamiaceae), collected in Ecuador. GC-FID and GC/MS analyses allowed the characterization and quantification of 79 components, representing 97.3% of the total sample. Sesquiterpene hydrocarbons (38.50%) and monoterpene hydrocarbons (30.59%) were found to be the most abundant volatiles, while oxygenated sesquiterpenes (16.20%) and oxygenated monoterpenes (2.10%) were the minor components. In order to better characterize the oil aroma, the most important odorants, from the sensorial point of view, were identified by Aroma Extract Dilution Analysis (AEDA) GC-O. They were α-Pinene, ß-Phellandrene, and Dauca-5,8-diene, exhibiting the characteristic woody, herbaceus, and earthy odors, respectively. Enantioselective GC analysis of L. mutica essential oil revealed the presence of twelve couples and two enantiomerically pure chiral monoterpenoids. Their enantiomeric excesses were from a few percent units to 100%. Moreover, the essential oil exhibited moderate in vitro activity against five fungal strains, being especially effective against M. canis, which is a severe zoophilic dermatophyte causal agent of pet and human infections.

Composition, Antifungal and Antiproliferative Activities of the Hydrodistilled Oils from Leaves and Flower Heads of Pterocephalus nestorianus Nábelek.

This article reports the first study of the chemical composition, and antifungal and antiproliferative properties of the volatile extracts obtained by hydrodistillation of the flower heads and leaves of the traditional Kurdish medicinal plant Pterocephalus nestorianus Nábelek, collected in the wild. A total of 55 constituents, 43 of the flower heads' oil (PFO) and 46 of the leaves' oil (PLO), respectively, were identified by GC/MS, constituting 99.68% and 99.04% of the two oils, respectively. The oils were obtained in 0.15% and 0.10% yields (w/w), respectively, on air-dried vegetable material. The prevalent constituents of the PFO were α-terpineol (2.41%), α-linalool (6.42%), 6,10,14-trimethylpentadecan-2-one (2.59%), myristic acid (24.65%), and lauric acid (50.44%), while the major components of PLO were (E)-hex-2-enal (2.26%), (E)-hex-2-en-1-ol (2.04), myristic acid (34.03%), and lauric acid (50.35%). The two oils showed significant inhibitory and fungicidal activities against the medically important fungi Candida albicans, Candida tropicalis, Microsporum canis, and Trichophyton mentagrophytes, with minimum inhibitory concentration ranging from 0.7 to 3.3 mg/ml and minimum fungicidal concentration varying from 1.4 to 6.6 mg/ml. The antiproliferative activity of the two oils was assayed against one normal and six human tumor cell lines. Both oils showed selective cytotoxic activity, with IC50 values ranging from 1.4 to 3.3 µg/ml.