Β-caryophyllene Epoxide Research Articles

Molecular docking analysis on 16 therapeutic ligands of Ocimum tenuiflorum L. (Tulasi) and their prospects in drug design for COVID-19

The PyRx software and Discovery studio were used in the present molecular docking studies of the 16 ligands of Ocimum tenuiflorum L., selected based on their high therapeutic potentials, viz., (E)-6-hydroxy-4,6-dimethylhept-3-en-2-one, Apigenin, Bieugenol, Cirsilineol, Cirsimaritin, β-Caryophyllene epoxide, Dehydrodieugenol B, Eugenol, Ferulaldehyde, Isothymonin, Isothymusin, Linalool, Luteolin, Ocimarin, Rosmarinic acid, and Thymol. Saquinavir was used as a positive control. The binding affinities of the 16 ligands to the main proteases of COVID-19 6LU7 and 6Y2E (critical for viral replication) and their ability to arrest the virus replication were recorded. The binding affinities of the ligands to 6LU7 and 6Y2E ranged from -4.3 and -4.7 kcal/mol (for (E)-6-hydroxy-4,6-dimethylhept-3-en-2-one) to -7.6 (for Rosmarinic acid to both target proteins). While the corresponding values for the control drug Saquinavir were -7.8 and -7.6 respectively. The Rosmarinic acid, in binding with both the proteases (-7.6 and -7.6 kcal/mol) showed six conventional hydrogen bonds, one carbon hydrogen bond (ASP 153 had one conventional hydrogen bond and one carbon hydrogen bond), one Pi-alkyl bond, one Pi-Pi stacked bond, eight van der waals bonds for 6LU7 protease; it formed three conventional hydrogen bonds, two Pi-alkyl bonds, one unfavourable donor – donor bond and 14 van der waals bonds with 6Y2E protease. The control drug – Saquinavir in binding with 6LU7 protease showed 12 van der waals, one alkyl, one Pi-alkyl, one Pi-cation, one Pi-stacked and four conventional hydrogen bonds, which indicates that it has less affinity when compared with Rosmarinic acid. Similarly, the control drug on binding with 6Y2E protease exhibited ten van der waals, four Pi-alkyl, one cation and three hydrogen bonds. The results are in conformity to similar other studies, and herald a promising scope for Rosmarinic acid as lead molecule in the drug discovery for COVID-19.

Ionic liquid-modulated aerobic oxidation of isoeugenol and β-caryophyllene via nanoscale Cu-MOFs under mild conditions

Novel synergistic systems based on Cu-1,3,5-benzenetricarboxylate and ionic liquid are developed for the convenient conversion of renewable olefins, isoeugenol and β-caryophyllene, under very mild conditions (i.e. 313 K and 1 atm O2). Using acidic ionic liquid [C4mim][HSO4] (5.0 mol%) as co-catalyst, Cu3(BTC)2-Lauric acid (LA) afforded high selectivity (95.8%) and excellent yield (86.3%) for vanillin methyl ketone during the aerobic oxidation of isoeugenol. In comparison, 91.1% selectivity for vanillin together with 28.9% conversion of isoeugenol was obtained over Cu3(BTC)2-LA in the presence of amino acid ionic liquid, [C4mim][Ala]. Additionally, 91.3% selectivity and 86.5% yield for β-caryophyllene epoxide were provided by Cu3(BTC)2-LA with the aid of neutral [C4mim]Cl (5.0 mol%), indicating the importance of different types of ILs in tuning the microenvironments of designed Cu3(BTC)2-LA nanosystems. Simultaneously, Cu3(BTC)2-LA/IL showed superior stability during above-mentioned transformations, as verified by TEM, FT-IR and XRD analyses. Insights into the synergistic free radical routes were supported by fluorescence and DRUV-Vis characterizations.

Phytochemical Analysis, α-Glucosidase and Amylase Inhibitory, and Molecular Docking Studies on Persicaria hydropiper L. Leaves Essential Oils.

Objective Medicinal plants and essentials oils are well known for diverse biological activities including antidiabetic potential. This study was designed to isolate essential oils from the leaves of Persicaria hydropiper L. (P. hydropiper), perform its phytochemical analysis, and explore its in vitro antidiabetic effects. Materials and Methods P. hydropiper leaves essential oils (Ph.Los) were extracted using a hydrodistillation apparatus and were subjected to phytochemical analysis using the gas chromatography mass spectrometry (GC-MS) technique. Ph.Lo was tested against two vital enzymes including α-glucosidase and α-amylase which are important targets in type-2 diabetes. The identified compounds were tested using in silico approaches for their binding affinities against the enzyme targets using MOE-Dock software. Results GC-MS analysis revealed the presence of 141 compounds among which dihydro-alpha-ionone, cis-geranylacetone, α-bulnesene, nerolidol, β-caryophyllene epoxide, and decahydronaphthalene were the most abundant compounds. Ph.Lo exhibited considerable inhibitory potential against α-glucosidase enzyme with 70% inhibition at 1000 μg mL−1 which was the highest tested concentration. The inhibitory activity of positive control acarbose was 77.30 ± 0.61% at the same tested concentration. Ph.Lo and acarbose exhibited IC50 of 170 and 18 µg mL−1 correspondingly. Furthermore, dose-dependent inhibitions were observed for Ph.Lo against α-amylase enzyme with an IC50 of 890 μg mL−1. The top-ranked docking conformation was observed for β-caryophyllene epoxide with a docking score of -8.3182 against α-glucosidase, and it has established seven hydrogen bonds and one H-pi interaction at the active site residues (Phe 177, Glu 276, Arg 312, Asp 349, Gln 350, Asp 408, and Arg 439). Majority of the identified compounds fit well in the binding pocket of Tyr 62, Asp 197, Glu 233, Asp 300, His 305, and Ala 307 active residues of α-amylase. β-Caryophyllene epoxide was found to be the most active inhibitor with a docking score of -8.3050 and formed five hydrogen bonds at the active site residues of α-amylase. Asp 197, Glu 233, and Asp 300 active residues were observed to be making polar interactions with the ligand. Conclusions The current study revealed that Ph.Lo is rich in bioactive metabolites which might contribute to its enzyme inhibitory potential. Inhibition of these enzymes is the key target in reducing postprandial hyperglycemia. However, further detailed in vivo studies are required for their biological and therapeutic activities.

An ultrathin amino-acid based copper(II) coordination polymer nanosheet for efficient epoxidation of β-caryophyllene

• CuIle-e nanosheet and CuIle-m nanoshuttle were fabricated from natural amino acid. • Stable catalytic systems, CuIle-e /acetone/TBHP and CuIle-e /THF/O 2 /TBHP, were built. • Good yields (86.1% or 87.2%) for β-caryophyllene epoxide were achieved. • Superior recyclability of CuIle-e nanosheet was realized. Natural amino acids are important building blocks for the construction of intriguing coordination polymers (CPs) because of their abundance, inexpensiveness and environmental benignness. Herein, two copper(II) CPs, namely, 2D CuIle-e nanosheet ( e : ethanol) and 1D CuIle-m nanoshuttle ( m : methanol), were fabricated from L -isoleucine ( Ile ) and well characterized with single-crystal x-ray diffraction, XPS spectra, TEM and AFM, etc. More importantly, two novel and stable catalytic nanosystems, i.e. CuIle-e /acetone/TBHP ( tert-butyl hydroperoxide) and CuIle-e /THF/O 2 /TBHP, were thus conveniently built by using ultrathin 2D CuIle-e nanosheet (~ 2.3 nm) in suitable aprotic solvents. Under mild conditions, complete conversion of β-caryophyllene and good yields (86.1% or 87.2%) for β-caryophyllene epoxide were gained via CuIle-e /acetone/TBHP or CuIle-e /THF/O 2 (1 atm)/TBHP (10.0 mol%), respectively. Notably, ultrathin CuIle-e nanosheet showed fairly satisfactory stability, which may open a unique window for the facile fabrication of new amino-acid based CP nanosystems with outstanding catalytic performances in actual applications. Two amino acid-based ultrathin CP nanosystems, CuIle-e /acetone/TBHP and CuIle-e /THF/1 atm O 2 /TBHP, were employed for the highly efficient epoxidation of β-caryophyllene under mild conditions.

Ionic liquid-mediated catalytic oxidation of β-caryophyllene by ultrathin 2D metal-organic framework nanosheets under 1 atm O2

An ionic liquid (IL)-mediated facile method was established for the epoxidation of β-caryophyllene with molecular oxygen using ultrathin (∼3−6 nm) 2D Cu-, Co- or Ce-based MOF nanosheets. Under the optimum conditions, high selectivity (92.4%) and excellent yield (86.7%) for β-caryophyllene epoxide were obtained over ultrathin (∼5.5 nm) Cu-TCPP nanosheets (TCPP = tetrakis(4-carboxyphenyl)porphyrin) with the aid of [C12mim]Cl at 313 K and 1 atm O2. Notably, a small amount of [C12mim]Cl (1-dodecyl-3-methylimidazolium chloride, 5.0 mol %) played pivotal roles in forming a favorable microenvironment in-situ, thus significantly improving the catalytic performances of above-mentioned Cu-TCPP nanosheets containing PVP stabilizer. Moreover, ultrathin Cu-TCPP nanosheets showed better stability during β-caryophyllene transformation in the presence of amphiphilic [C12mim]Cl, as supported by TEM and XRD analyses. Importantly, the addition of TBHP (tert-butyl hydroperoxide, 13.0 mol %) initiator is also crucial for the aerobic oxidation of β-caryophyllene viaCu-TCPP nanosheets/[C12mim]Cl/TBHP/O2 nanosystem. Further insights into the synergistic effects and free radical mechanism were achieved by fluorescence, DRUV-Vis, UV-vis and XPS measurements.

Dietary administration of β-caryophyllene and its epoxide to Sprague-Dawley rats for 90 days

Two independent 90-day GLP-compliant studies were conducted in Sprague-Dawley rats with β-caryophyllene or β-caryophyllene epoxide, two common flavoring and fragrance materials. Dietary concentrations of β-caryophyllene were 3500; 7000; and 21,000 ppm for males and 3500; 14,000; and 56,000 ppm for females. Dietary concentrations of β-caryophyllene epoxide were 1750; 10,500; and 21,000 ppm. There were no deaths or clinical toxicity attributable to either substance administration. Statistically significant, dose-dependent reductions in body weight, body weight gain, food consumption, and food efficiency at the highest dietary concentrations of β-caryophyllene, but not of β-caryophyllene epoxide, were attributed to palatability issues. Neither β-caryophyllene nor β-caryophyllene epoxide influenced estrus cyclicity or sperm parameters. Macroscopic and microscopic findings were primarily related to changes in the kidneys of male rats, consistent with α2u-globulin nephropathy, and in the liver of male and female rats, including hepatocyte hypertrophy at the middle and high intake levels. These changes correlated with increased absolute and relative organ weights. Since the kidney findings were a species- and sex-specific effect, the NOAEL in each study was based on hepatocyte hypertrophy at the two highest dietary concentrations and were determined to be 222 mg/kg bw/day for β-caryophyllene and 109 mg/kg bw/day for β-caryophyllene epoxide.

Essential Oil and Ethanol Extract of Oregano (Origanum vulgare L.) from Armenian Flora as a Natural Source of Terpenes, Flavonoids and other Phytochemicals with Antiradical, Antioxidant, Metal Chelating, Tyrosinase Inhibitory and Antibacterial Activity.

Origanum vulgare is used in Armenian cuisine as well as in folk medicine. The aim of this investigation was to determine the peculiarities of the chemical composition of Armenian flora's oregano essential oil (EO) and ethanol extract (EE) and to characterize mainly antioxidant and antibacterial properties in vitro. EO of plant aerial parts was extracted by the hydro-distillation method, and the composition was analyzed by gas-chromatography (GC). EE was prepared using ethanol as a solvent. Antioxidant, antibacterial and other biological activity of EO and EE was determined using appropriate methods. The terpenes were found to be the greatest part of oregano EO (β-caryophyllene epoxide - 13.3 %; β- caryophyllene -8.2 %; ο-cymene - 5.2 %). The flavonoid content of EE was 3.9±0.7 mg g-1 catechin equivalents. Antiradical activities of EO and EE expressed with half-maximum inhibitory concentrations were 1057 µg mL-1 and 19.97 µg mL-1. The antioxidant index in the case of using extract (1000 µg mL-1) was 77.3±1.5 %. The metal chelating activity of EE was 74.5±0.2 %. The tyrosinase inhibitory activities of EO, EE and arbutin were 26.5±0.3 %, 6.5±0.2 % and 50±0.1 %, respectively. Both EO and EE of oregano were able to suppress the growth of testmicroorganisms including clinical pathogen isolates, but have moderate antimicrobial activity. EO antibacterial activity against ampicillin-resistant Escherichia coli was similar to the activity against non-resistant strain. EE was not active against ampicillin-resistant E. coli in contrast to non-resistant one. The results indicate high antioxidant and moderate antibacterial as well as high antiradical, metal chelating, tyrosinase inhibitory activity of oregano EO and EE, which can be used as a natural source of terpenes, flavonoids and other phytochemicals in medicine, pharmaceutics, cosmetics and food industry. EO has antibacterial activity also against ampicillin-resistant E. coli.

Electron transfer-initiated epoxidation and isomerization chain reactions of β-caryophyllene.

The abundant sesquiterpene β-caryophyllene can be epoxidized by molecular oxygen in the absence of any catalyst. In polar aprotic solvents, the reaction proceeds smoothly with epoxide selectivities exceeding 70 %. A mechanistic study has been performed and the possible involvement of free radical, spin inversion, and electron transfer mechanisms is evaluated using experimental and computational methods. The experimental data-including a detailed reaction product analysis, studies on reaction parameters, solvent effects, additives and an electrochemical investigation-all support that the spontaneous epoxidation of β-caryophyllene constitutes a rare case of unsensitized electron transfer from an olefin to triplet oxygen under mild conditions (80 °C, 1 bar O2 ). As initiation of the oxygenation reaction, the formation of a caryophyllene-derived radical cation via electron transfer is proposed. This radical cation reacts with triplet oxygen to a dioxetane via a chain mechanism with chain lengths exceeding 100 under optimized conditions. The dioxetane then acts as an in situ-formed epoxidizing agent. Under nitrogen atmosphere, the presence of a one-electron acceptor leads to the selective isomerization of β-caryophyllene to isocaryophyllene. Observations indicate that this isomerization reaction is a novel and elegant synthetic pathway to isocaryophyllene.

The Strained Sesquiterpene β‐Caryophyllene as a Probe for the Solvent‐Assisted Epoxidation Mechanism

In our attempt to synthesize β-caryophyllene oxide in food-compatible conditions, we observed the uncatalyzed and highly selective epoxidation of β-caryophyllene, a strained bicyclic sesquiterpene, in ethanol with aqueous H2 O2 under radical-suppressing conditions without the addition of a catalyst. The unusual reactivity of β-caryophyllene allowed us to use it as a probe for the mechanism of the solvent-assisted epoxidation in a wide range of organic solvents. A kinetic study was performed to investigate the epoxidation mechanism; an excellent correlation was found between the observed epoxidation rates in different solvents and the Abraham's hydrogen bond formation parameters of these solvents. By means of computational analysis, it was found that the main role of the solvent consists of the stabilization of the elongated OO bond of H2 O2 in the transition state through hydrogen-bond donation to the leaving OH moiety of H2 O2 . α-Humulene was found to possess similar reactivity as β-caryophyllene whereas isocaryophyllene-the unstrained isomer of β-caryophyllene-was unreactive.

CHEMO-ENZYMATIC EPOXIDATION OF β-CARYOPHYLLENE USING LIPASES IMMOBILIZED IN AGAR GEL

The immobilization of enzymes and microorganisms on solid supports has been developed in recent years. These biocatalysts may be used in organic media allowing their storage and reuse, thus reducing costs of the process. Herein, lipases from various sources were immobilized in agar gel and used as catalysts in the chemo-enzymatic epoxidation of β-caryophyllene. Several experimental parameters, such as the use of different organic solvents including ionic liquids, time, temperature, and agitation rate were evaluated. The mono-epoxide was obtained as a single product. The best result was achieved using immobilized F-AP15 lipase, forming the corresponding β-caryophyllene epoxide at a conversion of 96% in an 8h reaction at 35 oC.

Antifungal impact of volatile fractions of Peumus boldus and Lippia turbinata on Aspergillus section Flavi and residual levels of these oils in irradiated peanut

To investigate the antifungal properties of essential oil (EO) vapors from boldo and poleo on Aspergillus section Flavi and the residual levels of the oils in peanut, irradiated peanuts conditioned at three water activities (0.98, 0.95, 0.93) were treated with 2 and 3μL/g of boldo and 3 and 5μL/g of poleo. EO treatments produced the greatest impact on fungal growth parameters, followed by oil concentrations and aW levels. The three main components in peanut exposed to oil vapors were piperitone oxide, α-terpinene and eucalyptol for boldo and β-caryophyllene epoxide, limonene and piperitenone for poleo. Residues of boldo and poleo EO were significantly decreased from 24.7 to 100% and from 26.6 to 99.7% at the end of the incubation period, respectively.The application of nontoxic boldo oil as fumigant in the control of Aspergillus section Flavi may represent a potential alternative antifungal treatment, without significant residues after 35days.

Enzymatic epoxidation of β-caryophyllene using free or immobilized lipases or mycelia from the Amazon region

• The chemo-enzymatic epoxidation of β-caryophyllene was studied. • The reactions were carried out under mild conditions. • Commercial and native lipases were used to produce the peroxy acids in situ . • The organic solvent was one of the most important parameters, and it is possible to obtain a single product. The chemo-enzymatic epoxidation of the terpene β-caryophyllene is reported herein. This compound can form two products, the mono-epoxide 2 and the di-epoxide 3 . Different experimental conditions, varying the source of the lipases (including mycelia from the Amazon region), the oxidizing agents (H 2 O 2 aq. (AHP) or urea-hydrogen peroxide (UHP)) and the substituted acyl donors on the alkyl chain (bromide and alkyl), along with the influence of organic medium, were evaluated. Depending on the experimental conditions the formation of a single product could be obtained. CAL-B was the most efficient catalyst (conv. >99%). When using the commercial lipases product 2 was obtained in conversions of 16–27%, and using the native lipases 2 was obtained in conversions of 20–23%. With the use of mycelia UEA_06 and UEA_53 the conversions were 16 and 21%, respectively. When the 2-bromo alkylated and 2-ethylhexanoic acids were used as acyl donors only the mono-epoxide 2 was obtained in conversions of 14–54% (24 h). AHP was found to be a better oxidizing agent than UHP, a shorter time and lower amount being required to obtain 2 or 3 as the sole product in good conversions (60 up to >99%). The organic solvents were also selective. When using n -hexane the preferred formation of 2 was observed with >99% conversion, and when ethyl acetate or toluene were used the conversion to 3 was also >99% (in 8 and 24 h, respectively).

Synthesis of (−)-β-caryophyllene oxide via regio- and stereoselective endocyclic epoxidation of β-caryophyllene with Nemania aenea SF 10099-1 in a liquid–liquid interface bioreactor (L–L IBR)

Nemania aenea SF 10099-1, a basidiomycete isolated from a forest soil sample, regio- and stereoselectively epoxidized β-caryophyllene (Car) to (-)-β-caryophyllene oxide (Car-Ox) in a liquid-liquid interface bioreactor (L-L IBR) consisted of a liquid medium (a bottom phase), a fungus-ballooned microsphere (MS) mat (a middle phase), and an organic phase containing Car (a top phase). The cultivation conditions, such as carbon and nitrogen sources, kind of MS, initial medium pH and Car concentration, were optimized in the L-L IBR system. The best carbon and nitrogen sources were xylose and tryptone, respectively. The most suitable polyacrylonitrile MS was MMF-DE-1 (former MFL-80SDE; non-coated type). Although the strain could not grow below pH 5.5, the endocyclic epoxidation of Car efficiently proceeded at a wide range of initial medium pH (6.0 to 9.0). The bioconversion system exhibited an excellent alleviation effect toward substrate and product inhibitions. While Car could be added into an organic phase (KF-96L-1CS, dimethyl silicone oil) at 50% (w/v), the accumulation of Car-Ox reached over 30g/l in spite of these strong microbial toxicities. Moreover, the epoxidation reaction smoothly proceeded in a novel L-L IBR system, a multistory L-L IBR systems, consisted of 5 stacked reactor units. The optical rotation of Car-Ox produced was (-) and the enantiomeric excesses of (-)-β-Car-Ox purified by 1st and 2nd recrystallization from methanol reached 97.51 and 99.33%, respectively.

GC–MS Combined with Chemometrics for Analysis of the Components of the Essential Oils of Sweet Potato Leaves

Essential oils from the leaves of two cultivars of sweet potato have been investigated by gas chromatography–mass spectrometry with the help of two chemometric resolution methods, heuristic evolving latent projections and selective ion analysis, and use of temperature-programmed retention indices. The overall volume integration technique was used for quantitative analysis. Eighty-four and forty-five components, accounting for 89.39 and 98.08% of the oils, were tentatively identified in the two cultivars. Thirty-four components were identical in both cultivars. Major constituents of Shuiguo were germacrene D (21.83%), germacrene B (15.17%), caryophyllene (12.44%), and n-hexadecanoic acid (11.24%). Caryophyllene (28.73%), γ-muurolene (13.07%), and β-caryophyllene epoxide (9.04%) were the major components of Xiangshu-17. These results indicate the method is suitable for analysis of the two-dimensional data obtained from essential oils.

Sesquiterpenes from Culcasia scandens P. Beauv.

From Culcasia scandens P. Beauv., carota-4(5), 11(12)-diene (isodaucene), carota-3(4), 11(12)-dien-5-one, a new epoxide, 4,5-epoxy-carota-11(12)-ene (isodaucene epoxide) and β-caryophyllene epoxide were isolated. The structures were established spectroscopically. Epoxidation of isodaucene with m-CPBA confirmed the structure and stereochemistry of the new epoxide.

Chemical composition of the essential oils of twoSalvia species from Iran,Salvia virgata Jacq. andSalvia syriaca L.

The chemical composition of the essential oils of Salvia virgata Jacq. and Salvia syriaca L. growing wild in Iran were examined by GC and GC–MS. Fifteen components were characterized for S. virgata with β-caryophyllene (46.6%), germacrene B (13.9%), β-caryophyllene epoxide (13.2%), spathulenol (6.4%) and germacrene D (5.7%) as the major constituents. Twenty-two components were identified in the oil of S. syriaca, with germacrene-B (34.8%), germacrene-D (29.2%), α-ylangene (3.6%) and spathulenol (3.4%) as the major constituents. Copyright © 1999 John Wiley & Sons, Ltd.

Chemical composition of the essential oils of two Salvia species from Iran, Salvia virgata Jacq. and Salvia syriaca L.

The chemical composition of essential oils of Salvia virgata Jacq. and Salvia syriaca L. growing wild in Iran were examined by GC and GC-MS Fifteen components were characterized for S. virgata with β-caryophyllene (46.6%), germacrene B (13.9%), β-caryophyllene epoxide (13.2%), spathulenol (6.4%) and germacrene D (5.7%) as the major constituents, Twenty-two components were identified in the oil of S. syriaca, with germacrene -D (29.2%), α-ylangene (3.6%) and spathulaenol (3.4%) as the major constituents.

Aromatic plants of tropical central africa. Part VII. A comparative study of the volatile constituents of the stem bark of Enantia chlorantha oliv. and Xylopia staudtii engl. & diels from cameroon

AbstractHydrodistillation of the stem bark of Enantia chlorantha Oliv. and of Xylopia staudtii Engl. & Diels from Cameroon gave yellowish coloured oils in 0.2% yeild. The composition of the essential oils was determined by mean of capillary gas chromatogrphy and mass spectrometry. The volatile oils from the two species were found to be similar and very complex Oxygenated sesquiterpenes constitute more than 70% of the two samples, among which three epoxides (1,5‐epoxysalvial‐4(14)‐ene, β‐caryophyllene epoxide, humulene epoxide), spathulenol and α‐cadinol are the most prominent.

Constituents of Japanese Peppermint Oil

Isopentyl isovalerate and anisic acid were first isolated and identified from the Japanese peppermint oil. The former compound possesses characteristic apple-like oder. α-Bourbonene, menthofurolactone, and β-caryophyllene epoxide were also isolated and identified from the oil of Shubi, a newly registered Japanese peppermint.