Triplinones A-H: Anti-Inflammatory Arylalkenyl α,ß-Unsaturated-δ-Lactones Isolated from the Leaves of Australian Rainforest Plant Cryptocarya triplinervis (Lauraceae).

Our ongoing exploration of Australian rainforest plants for the biodiscovery of anti-inflammatory agents led to the isolation and structural elucidation of eight new arylalkenyl α,ß-unsaturated-δ-lactones, triplinones A-H (1-8), from the leaves of the Australian rainforest plant Cryptocarya triplinervis B. Hyland (Lauraceae). The chemical structures of these compounds were established by NMR spectroscopic data analysis, while their relative and absolute configurations were established using a combination of Mosher ester analysis utilizing both Riguera's and Kishi's methods, ECD experiments, and X-ray crystallography analysis. Compounds 1-8 exhibited good inhibitory activities toward nitric oxide (NO) production in lipopolysaccharide (LPS) and interferon (IFN)-γ induced RAW 264.7 macrophages, in particular compounds 1-3 and 5, with IC50 values of 7.3 ± 0.5, 6.0 ± 0.3, 5.6 ± 0.3, and 5.4 ± 2.5 µM, respectively.

Beyond the Bark: An Overview of the Chemistry and Biological Activities of Selected Bark Essential Oils.

Essential oils have been used by indigenous peoples for medicinal purposes since ancient times. Their easy availability played an important role. Even today, essential oils are used in various fields­be it as aromatic substances in the food industry, as an aid in antibiotic therapy, in aromatherapy, in various household products or in cosmetics. The benefits they bring to the body and health are proven by many sources. Due to their complex composition, they offer properties that will be used more and more in the future. Synergistic effects of various components in an essential oil are also part of the reason for their effectiveness. Infectious diseases will always recur, so it is important to find active ingredients for different therapies or new research approaches. Essential oils extracted from the bark of trees have not been researched as extensively as from other plant components. Therefore, this review will focus on bringing together previous research on selected bark oils to provide an overview of barks that are economically, medicinally, and ethnopharmaceutically relevant. The bark oils described are Cinnamomum verum, Cedrelopsis grevei, Drypetes gossweileri, Cryptocarya massoy, Vanillosmopsis arborea and Cedrus deodara. Literature from various databases, such as Scifinder, Scopus, Google Scholar, and PubMed, among others, were used.

Cryptocaryoic acids A - C: New phenyl alkyl acids isolated from the leaves of Australian rainforest plant Cryptocarya mackinnoniana.

Phytochemical investigation of the leaves of the Australian rainforest tree Cryptocarya mackinnoniana led to the discovery of three new oxygenated phenyl alkyl acids, cryptocaryoic acids A - C and two known compounds, cryptocaryone and 2',6'-dihydroxy-4'-methoxychalcone. The structures of all the compounds were determined by detailed spectroscopic analysis. Mosher's analysis was used for absolute stereochemistry determination at C-11, while the remaining stereochemistry determination of the one remaining stereocenter C-13 was based on NOESY correlations. All compounds isolated were also evaluated for their anti-inflammatory properties by assessing their inhibitory effects on LPS and interferon-γ induced nitric oxide (NO) production and TNF- α release in RAW 264.7 macrophages. The new cryptocaryoic acids exhibited weak to moderate anti-inflammatory activity (NO inhibition) ranging from (18.4-56 µM).

Two Novel Flavonoids and Cytotoxicity Evaluation from Cryptocarya yunnanensis.

Two new flavonoids, cryunchalcone (1) and cryptoyunnanone I (2), were isolated from the leaves and twigs of Cryptocarya yunnanensis. Their structures were elucidated by the detailed spectroscopic data analysis and electronic circular dichroism (ECD) calculations. Cryunchalcone (1) is a biflavonoid constructed by a dihydrochalcone coupled with a chalcone through an unprecedented C-2''-C-6 linkage. Cryptoyunnanone I (2) is a unique complex flavanone bearing a phenylpropanoid moiety.

Complex Flavanones from Cryptocarya metcalfiana and Structural Revision of Oboflavanone A.

Nine new complex flavanones, cryptometcones A-I (1-9), along with four known analogues, were isolated from Cryptocarya metcalfiana. The structures of 1-9 including their absolute configurations were elucidated by spectroscopic data analysis and electronic circular dichroism (ECD) calculations. In addition, the structure of oboflavanone A was revised, while the absolute configurations of oboflavanone B, cryptoflavanone C, and cryptoflavanone D were determined, according to their spectroscopic data. Compounds 3-5, 8, and 9 exhibited cytotoxicity against the HCT-116 cancer cell line.

α-Pyrones with glucose uptake-stimulatory activity from the twigs of Cryptocarya wrayi.

Five new α-pyrones, cryptowratones A-E (1-5), and five known congeners (6-10), together with four other known compounds 11-14 were isolated from the twigs of Cryptocarya wrayi. The structures of the new compounds were elucidated on the basis of extensive spectroscopic data analysis and ECD calculations. All α-pyrones except 6 were evaluated for their stimulatory effects on glucose uptake in vitro with CHO-K1/GLUT4 cells. The positive control insulin displayed an approximate 42 ± 0.14% promotion on glucose uptake at 25 µM, compared with the CHO-K1/GLUT4 group. Compounds 1a/2a, 2, 3, and 10 showed a more significant stimulation of glucose uptake than insulin (25 µM) by 36 ± 0.08%, 27 ± 0.12%, 28 ± 0.12%, and 25 ± 0.12% at 1.5 µM, respectively. Immunofluorescence assays indicated the glucose uptake-stimulatory activity of α-pyrones might be correlated with increased GLUT4 translocation.

Two new isoquinoline alkaloids from Cryptocarya wrayi and their biological activities.

Two new isoquinoline alkaloids, cryptowrayines A (1) and B (2), along with one known pavine alkaloid (-)-12-hydroxyeschscholtzidine (3), were isolated from the twigs of Cryptocarya wrayi. The structures of new compounds were elucidated by extensive spectroscopic data analysis and electronic circular dichroism (ECD) calculations. Both compounds 1 and 2 exhibited moderate quinone reductase inducing activity in Hepa 1c1c7 cells.

Cytotoxic α-pyrone derivatives from Cryptocarya yunnanensis.

Five new α-pyrone derivatives, cryptoyunnanes A - E (1 - 5), together with four known analogues, were isolated from the leaves and twigs of Cryptocarya yunnanensis. Their structures including absolute configurations were elucidated by extensive spectroscopic data and electronic circular dichroism (ECD) analyses. Compounds 4 and 6 showed significant cytotoxicity against A549, HCT-116, MDA-MB-231, PC-3 and HeLa with IC50 values from 2.25 to 8.97 µM. Compounds 1, 2 and 7 also displayed good cytotoxicity against HCT-116, MDA-MB-231 and PC-3 with IC50 values from 1.26 to 8.32 µM. This is the first time to report the isolation and bioactivity evaluation of chemical constituents from C. yunnanensis.

Ene-reductase transformation of massoia lactone to δ-decalactone in a continuous-flow reactor.

The demand for natural food flavorings increases every year. Biotransformation has become an attractive approach to obtain natural products. In this work, enantiomerically pure (R)-(+)-δ-decalactone was obtained by reduction of the C=C double bond of natural massoia lactone in a continuous-flow reactor. Of 13 different ene-reductases isolated, purified and tested, OYE3 was found to be the most efficient biocatalyst. The selected biocatalyst, either in the form of purified enzyme, cell lysate, whole cells or immobilized cells, was tested in the batch system as well as in the packed-bed flow bioreactor. The biotransformation performed in batch mode, using Ca2+-alginate immobilized cells of Escherichia coli BL21(DE3)/pET30a-OYE3, furnished the desired product with complete conversion in 30 min. The process was intensified using a continuous-flow reactor-membrane filtration system (flow 0.1 mL/min, substrate concentration 10 mM, pH 7, 24 °C) with cell lysate as biocatalyst combined with a cofactor regeneration system, which allowed obtaining > 99% bioconversion of massoia lactone.

Cryptoyunnanones A-H, Complex Flavanones from Cryptocarya yunnanensis.

Eight new complex flavanones with a novel linkage, cryptoyunnanones A-H (1-8), together with four known α-pyrones, were isolated from the leaves and twigs of Cryptocarya yunnanensis. The structures of 1-8 including their absolute configurations were characterized by spectroscopic data analysis and single-crystal X-ray crystallography. Plausible biosynthetic pathways for the formation of compounds 1-8 were proposed. Compounds 1-4 exhibited cytotoxicity against HCT-116, MDA-MB-231, and PC-3 cancer cells with IC50 values from 6.4 to 9.1 µM.

Cytotoxic lignans from Cryptocarya impressinervia.

Chemical investigation of the twigs of Cryptocarya impressinervia yielded 23 known compounds including 8 lignans, 3 phenylpropionates, 1 xanthone, 3 flavonoids, 1 phenylpropanoid, 1 substitued phenol, 1 triterpenoid, 3 sterols and 2 aliphatic compounds. All the compounds was isolated from C. impressinervia for the first time. 9,9'-O-Di-feruloyl-(-)-secoisolariciresinol (1) displayed significant cytotoxic activities on five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7 and SW-480), with IC50 values of 3.58, 4.55, 6.39, 5.09 and 4.80 µM, respectively. Rhusemialin A (2) showed significant activity against HL-60 with IC50 of 3.69 µM. Dihydrosinapyl ferulate (3) displayed moderate cytotoxic activities against five tested human cancer cell lines. To the best of our knowledge, this is the first report on the constituents of C. impressinervia and cytotoxic activities of compounds 1-3 on the tested cancer cell lines.

The Chemical Compositions of Essential Oils Derived from Cryptocarya alba and Laurelia sempervirens Possess Antioxidant, Antibacterial and Antitumoral Activity Potential.

Cryptocarya alba (Peumo; CA) and Laurelia sempervirens (Laurel; LS) are herbs native to the Chilean highlands and have historically been used for medicinal purposes by the Huilliches people. In this work, the essential oils were extracted using hydrodistillation in Clevenger apparatus and analyzed by GC-MS to determine their composition. The antioxidant capacity (AC) was evaluated in vitro. The cytotoxicity was determined using cell line cultures both non tumoral and tumoral. The toxicity was determined using the nematode Caenorhabditis elegans. The antimicrobial activity was evaluated against 52 bacteria using the agar disc diffusion method and the minimum inhibitory concentrations (MICs) were determined. The principal compounds found in C. alba essential oil (CA_EO) were α-terpineol (24.96%) and eucalyptol (21.63%) and were isazafrol (91.9%) in L. sempervirens essential oil (LS_EO). Both EOs showed antioxidant capacity in vitro. Both EO showed antibacterial activity against bacteria using. LS_EO showed more inhibitory effect on these cell lines respect to CA_EO. Both EOs showed toxicity against the nematode C.elegans at 3.12-50 mg/mL. The essential oils of CA and LS have an important bioactive potential in their antioxidant, antibacterial and cytotoxicity activity. Both essential oils could possibly be used in the field of natural medicine, natural food preservation, cosmetics, sanitation and plaguicides among others.

Essential oil composition of three Cryptocarya species from Malaysia.

Cryptocarya species are mainly distributed in Africa, Asia, Australia and South America, widely used in traditional medicines for the treatment of skin infections and diarrhea. The present investigation reports on the extraction by hydrodistillation and the chemical composition of three Cryptocarya species (Cryptocarya impressa, Cryptocarya infectoria, and Cryptocarya rugulosa) essential oils from Malaysia. The chemical composition of these essential oils was fully characterized by gas chromatography (GC-FID) and gas chromatography-mass spectrometry (GC-MS). A total of 51 components were identified in C. impressa, C. infectoria, and C. rugulosa essential oils representing 91.6, 91.4, and 83.0% of the total oil, respectively. The high percentages of α-cadinol (40.7%) and 1,10-di-epi-cubenol (13.4%) were found in C. impressa oil. ß-Caryophyllene (25.4%) and bicyclogermacrene (15.2%) were predominate in C. infectoria oil. While in C. rugulosa oil, bicyclogermacrene (15.6%), δ-cadinene (13.8%), and α-copaene (12.3%) were predominate. To the best of our knowledge, there is no report on the essential oil composition of these three species.

5,6-Dihydro-α-pyrones from the leaves of Cryptocarya pulchinervia (Lauraceae).

Three new 5,6-dihydro-α-pyrones derivatives, named (S)-rugulactone (1) pulchrinervialactone A (2), and pulchrinervialactone B (4), along with one known pyrone, cryptobrachytone C (3), and three known amide derivatives (5-7) have been isolated from the leaves of Cryptocarya pulchrinervia. The structures of 1-7 were elucidated based on extensive spectroscopic data and comparison with literatures. The configurations of compounds 3 and 4 were established by single crystal X-ray diffraction analysis. This is also the first report in finding (S)-rugulactone (1) as a natural product. In addition, the preliminary cytotoxic activity of the isolated compounds was evaluated against P-388 cells using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. All the pyrones, except compound 4, were active significantly inhibiting the growth of P-388 cells, while the amides derivatives (5-7) showed moderate to weak activities. Therefore, compounds 1-3 could be potentially examined further for anticancer agents.

Evaluation of the efficacy and toxicity of massoia oil nanoemulsion.

In order to enhance essential oil's stability and water insolubility, Massoia aromatica oil nanoemulsion was formulated and tested on the planktonic growth and biofilm formation of Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans; macrophage phagocytosis and on Vero cells viability. Oil in water nanoemulsion formula was optimized by using several solvents and co-solvents composition. The stability test of the formula was conducted by using a six cycle's freeze-thaw technique. Particle size and morphology were analyzed using a particle size analyzer and transmission electron microscopy. Microbial growth, biofilm formation inhibition, and cytotoxicity assays were performed on the optimized formula by using micro dilution methods. Mice macrophage phagocytosis activities against latex and C. albicans in the presence of samples were evaluated. Massoia nanoemulsion was obtained as a transparent yellowish emulsion having 99.6-99.9% of transmittance; physically and chemically stable; showed stronger antibacterial and antibiofilm on P. aeruginosa and S. aureus, moderate to C. albicans; no significant different on phagocytic activities. The IC50 of massoia oil nanoemulsion and massoia oil towards Vero cells were 35.9µg/mL and 107.5µg/mL respectively. Massoia oil nanoemulsion can protect the stability and decreases the hydrophobicity of the oil, conserve the antimicrobial and immunomodulatory activities, but increases its cytotoxicity.

Spiro[3.5]nonenyl Meroterpenoid Lactones, Cryptolaevilactones G-L, an Ionone Derivative, and Total Synthesis of Cryptolaevilactone M from Cryptocarya laevigata.

A CH3OH-CH2Cl2 (1:1) extract (N025439) of the leaves and twigs of Cryptocarya laevigata furnished eight new compounds, 1-8. Based on extensive 1D and 2D NMR spectroscopic data examination, the new δ-lactone derivatives 1-6 are monoterpene-polyketide hybrids containing a unique spiro[3.5]nonenyl moiety. Their trivial names, cryptolaevilactones G-L, follow those of the related known meroterpenoids cryptolaevilactones A-F. Cryptolaevilactone L (6) contains 11,12-cis-oriented substituents, while the other cryptolaevilactones contain trans-oriented groups. The structure of the linear δ-lactone 7, cryptolaevilactone M, was characterized from various spectroscopic data analysis, and the absolute configuration was determined by total synthesis through stereoselective allylation and Grubbs olefin metathesis. Compound 8 was elucidated to be an ionone derivative with a 3,4-syn-diol functionality.

Antichemotactic and Antifungal Action of the Essential Oils from Cryptocarya aschersoniana, Schinus terebinthifolia, and Cinnamomum amoenum.

The purpose of this work was to determine the chemical composition and evaluate the antichemotactic, antioxidant, and antifungal activities of the essential oil obtained from the species Cryptocarya aschersoniana Mez, Cinnamomum amoenum (Ness & Mart.) Kosterm., and Schinus terebinthifolia Raddi, as well as the combination of C. aschersoniana essential oil and terbinafine against isolates of dermatophytes. Allo-aromadendrene, bicyclogermacrene, and germacrene B were identified as major compounds in essential oils. The essential oil of C. aschersoniana shown 100 % inhibitory effect on leukocyte migration at the concentration of 10 µg/mL while S. terebinthifolia oil presented 80.1 % inhibitory effect at the same concentration. Only S. terebinthifolia oil possessed free-radical-scavenging activity which indicates its antioxidant capacity. The essential oils were also tested against fungal isolates of dermatophyte species (Trichophyton rubrum, Trichophyton mentagrophytes, Microsporum canis and Microsporum gypseum), resulting in MIC ranging from 125 µg/mL to over 500 µg/mL. C. aschersoniana oil combined with terbinafine resulted in an additive interaction effect. In this case, the essential oil may act as a complement to conventional therapy for the topical treatment of superficial fungal infections, mainly because it is associated with an anti-inflammatory effect.

Cytotoxic arylalkenyl α,ß-unsaturated δ-lactones from Cryptocarya brachythyrsa.

Three new arylalkenyl α,ß-unsaturated δ-lactones, cryptobrachytones A-C (1-3), together with one known analogue kurzilactone (4), were isolated from the leaves and twigs of Cryptocarya brachythyrsa. Their structures were elucidated based on extensive spectroscopic data and electronic circular dichroism (ECD) analysis. All the isolates were evaluated in vitro for anti-proliferative activity against a panel of five human cancer cell lines and one human normal cell, respectively, and the results showed 1, 2 and 4 possessing significant selective cytotoxicity toward the human cancer cell lines with IC50 values from 5.41 to 15.43 µM. This is the first study for C. brachythyrsa.

Assessing the effectiveness of green synthetized silver nanoparticles with Cryptocarya alba extracts for remotion of the organic pollutant methylene blue dye.

In the present work, silver nanoparticles (AgNPs) synthetized with Cryptocarya alba (Peumo) leaf extract were studied. The fabrication method was fast, low cost, and eco-friendly, and the final properties of AgNPs were determined by experimental parameters, such as AgNO3 and Peumo extract concentrations used. Setting suitable experimental conditions, crystalline AgNPs with apparent spherical forms and average diameter around 3.5 nm were obtained. In addition, the capability of synthesized Peumo-AgNPs to remove methylene blue dye (MB) in aqueous solution as well as their catalytic effectiveness was also investigated. The results showed that green synthesized AgNPs can remove fast and effectively the MB dye from aqueous medium by itself, but better results were found acting like catalyst by using sodium borohydride (NaBH4) in the reaction. In addition, this green nanomaterial can be recycling several times maintaining initial properties for removal of MB. Thus, AgNPs synthetized with Peumo leaf extracts could be an excellent catalyst candidate for degradation of blue methylene dye in chemical industries.

Selected α-pyrones from the plants Cryptocarya novoguineensis (Lauraceae) and Piper methysticum (Piperaceae) with activity against Haemonchus contortus in vitro.

Due to the widespread occurrence and spread of anthelmintic resistance, there is a need to develop new drugs against resistant parasitic nematodes of livestock animals. The Nobel Prize-winning discovery and development of the anti-parasitic drugs avermectin and artemisinin has renewed the interest in exploring natural products as anthelmintics. In the present study, we screened 7500 plant extracts for in vitro-activity against the barber's pole worm, Haemonchus contortus, a highly significant pathogen of ruminants. The anthelmintic extracts from two plants, Cryptocarya novoguineensis and Piper methysticum, were fractionated by high-performance liquid chromatography (HPLC). Subsequently, compounds were purified from fractions with significant biological activity. Four α-pyrones, namely goniothalamin (GNT), dihydrokavain (DHK), desmethoxyyangonin (DMY) and yangonin (YGN), were purified from fractions from the two plants, GNT from C. novoguineensis, and DHK, DMY and YGN (= kavalactones) from P. methysticum. The three kavalactones induced a lethal, eviscerated (Evi) phenotype in treated exsheathed third-stage larvae (xL3s), and DMY and YGN had moderate potencies (IC50 values of 31.7 ±â€¯0.23 µM and 23.7 ±â€¯2.05 µM, respectively) at inhibiting the development of xL3s to fourth-stage larvae (L4s). Although GNT had limited potency (IC50 of 200-300 µM) at inhibiting L4 development, it was the only compound that reduced L4 motility (IC50 of 6.25-12.50 µM). The compounds purified from each plant affected H. contortus in an irreversible manner. These findings suggest that structure-activity relationship studies of α-pyrones should be pursued to assess their potential as anthelmintics.