Monoterpene Derivatives Research Articles

Minor monoterpene derivatives from an aqueous extract of the hook-bearing stem of Uncaria rhynchophylla

Seven new minor monoterpene derivatives (1–7), together with six known analogues, were isolated from an aqueous decoction of the hook-bearing stems of Uncaria rhynchophylla (Gou-teng). Their structures were determined by spectroscopic data analysis and electronic circular dichroism (ECD) calculations, of which 1 was confirmed by single crystal X-ray diffraction.

Combination of GC-MS Molecular Networking and Larvicidal Effect against Aedes aegypti for the Discovery of Bioactive Substances in Commercial Essential Oils.

Dengue is a neglected disease, present mainly in tropical countries, with more than 5.2 million cases reported in 2019. Vector control remains the most effective protective measure against dengue and other arboviruses. Synthetic insecticides based on organophosphates, pyrethroids, carbamates, neonicotinoids and oxadiazines are unattractive due to their high degree of toxicity to humans, animals and the environment. Conversely, natural-product-based larvicides/insecticides, such as essential oils, present high efficiency, low environmental toxicity and can be easily scaled up for industrial processes. However, essential oils are highly complex and require modern analytical and computational approaches to streamline the identification of bioactive substances. This study combined the GC-MS spectral similarity network approach with larvicidal assays as a new strategy for the discovery of potential bioactive substances in complex biological samples, enabling the systematic and simultaneous annotation of substances in 20 essential oils through LC50 larvicidal assays. This strategy allowed rapid intuitive discovery of distribution patterns between families and metabolic classes in clusters, and the prediction of larvicidal properties of acyclic monoterpene derivatives, including citral, neral, citronellal and citronellol, and their acetate forms (LC50 < 50 µg/mL).

Bioactive Compounds in Aegopodium podagraria Leaf Extracts and Their Effects against Fluoride-Modulated Oxidative Stress in the THP-1 Cell Line.

Aegopodium podagraria L. (goutweed), a member of the Apiaceae family, is a common perennial plant found all around the world that has been used in folk medicine since antiquity. Goutweed leaves contain polyacetylenes, essential oils, mono- and sesquiterpenes, vitamins, macro- and microelements, and phenolic compounds. In spite of its many health-promoting properties, including antioxidant effects, the plant has not been thoroughly studied. The aim of this study was to investigate the antioxidant properties of different goutweed leaf extracts and their effects on the THP-1 cell line, and also to describe the chemical characteristics of goutweed. Falcarinol and falcarindiol and essential oil were determined by gas chromatography coupled with mass spectrometry. Spectrophotometry was used to measure the total content of polyphenols and antioxidant activity–by DPPH and FRAP methods. Oxidative stress in THP-1 cells was induced via sodium fluoride. Then, goutweed leaf extracts were added to evaluate their influence on antioxidant potential (ABTS) and the activity of antioxidant enzymes. Confocal microscopy was used to visualise the production of cytoplasmic and mitochondrial reactive oxygen species (ROS) and for in vitro imaging of apoptosis. The ethanol extracts have a high total content of polyphenols, polyacetylenes, and essential oil, as well as high antioxidant potential. The main volatiles represented diverse chemical groups, which are both oxygenated derivatives of sesquiterpenes and monoterpenes. We also demonstrated positive effects of the high antioxidant potential and increased activity of antioxidant enzymes on cell cultures under severe fluoride-induced oxidative stress. Extraction at 80 ℃ and the use of ethanol as a solvent increased the antioxidant capacity of the extract. The leaves of Aegopodium podagraria may serve as a valuable source of antioxidants in the daily diet and assist in the prevention and treatment of oxidative stress-mediated conditions, e.g., inflammatory conditions, cardiovascular diseases, neurodegenerative diseases, and even obesity.

Diaportones A-C: Three New Metabolites From Endophytic Fungus Diaporthe foeniculina BZM-15.

Phytochemical investigation of Diaporthe foeniculina BZM-15 led to one new γ-butyrolactone derivative, diaportone A (1), one cyclopentenone derivative, diaportone B (3), and one monoterpene derivative, diaportone C (5), along with six known compounds (2, 4, and 6–9). Their structures as well as the absolute configurations were characterized by means of NMR, HRESIMS, and ECD spectroscopy and quantum chemistry calculation, respectively. Furthermore, all compounds were evaluated for their cytotoxic activity and antibacterial activity, and compounds 7 and 8 displayed significant antiproliferative effects on three human cancer cell lines (SF-268, MCF-7, and HepG2) with IC50 values ranging from 3.6 to 15.8 μM.

The evidence of health benefits and food applications of Thymus vulgaris L.

T. vulgaris , commonly known as the thyme, is an aromatic plant belonging to the Lauraceae family. Six different chemotypes were described for T. vulgaris. The chemotypes are named after its dominant monoterpene: geraniol (G), α-terpineol (A), thuyanol-4 (U), linalool (L), carvacrol (C), and thymol (T). For this review, an extensive bibliographic research on Thymus vulgaris was carried out, including its main components both nutrients and bioactives. Botanical description, distribution and cultivation were also addressed as well as uses in folk medicine. Particular attention was given to biological activities, clinical studies, possible limitations and potential applications. T. vulgaris L. is used as food and for medicinal purposes and it has a great economic importance due to its composition on monoterpene derivatives including p-cymene, thymol and carvacrol. The value of T. vulgaris has been recognized by the pharmaceutical industry, because it proved to have hepatoprotective properties and to have effectiveness as e xpectorant agent , a nti-acne agent, and as fungicidal and antiviral drug. It has been also recognized by the industries of pests' repellents, foods, food packaging and cosmetics. This vast number of industrial applications is mainly due to its antioxidant, antimicrobial, anti-inflammatory and anticancer effects. • T. vulgaris is a natural product with numerous benefits for human health. • T. vulgaris can be used whole, ground or as an active extract or as essential oil (EO). • Applications of T. vulgaris include the pharmaceutical, cosmetic, repellent of pests and food and food packaging industries. • The most relevant biological activities are antioxidant, antimicrobial, anti-inflammatory and anticancer effects. • Despite T. vulgaris several established uses, very limited clinical studies have been performed.

Nitric oxide inhibitory terpenes and its glycosides from Ainsliaea bonatii

Seven new terpenes and its derivatives classified into a p-menthane glycoside (1), a guaianolide glycoside (2), three eudesmane and its glycosides (3–5), and two mono-terpene derivatives (9 and 10) were isolated from Ainsliaea bonatii, together with three known guaianolides (6–8). Their structures were elucidated by spectroscopic data analysis, and absolute configurations were determined by DP4+ probability analysis via calculated 13C NMR data of isomers. Compounds 6 and 9 showed nitric oxide (NO) inhibitory effects in LPS-induced RAW 264.7 macrophage cells with IC50 values of 9.3 and 10.6 μM, respectively.

The development of Origanum vulgare L. into nanoparticles in dosage forms

&#x0D; Introduction: Origanum vulagre L. is known for its abundant essential oil content with monoterpene and sesquiterpene derivatives. &#x0D; Aims: This research aims to gather comprehensive information about oregano and its potential to be developed into a nanotechnology drug delivery system. &#x0D; Methods: Literary studies were conducted using data obtained by searching through online literature sources. &#x0D; Results: Oregano is reported to contain active phytochemicals like esitronellol. In modern scientific literature, its extracts have been reported to have antidiabetic, analgesic, anti-inflammatory, anticancer and other potential properties. Further research needs to be done to ascertain the safety and therapeutic effect of this plant. The development of oregano’s essential oil into nanoparticles in dosage forms can increase its solubility, stability, and pharmacological effects.&#x0D;

Saponins are responsible for the anti-obesogenic activity of Acacia concinna

Acacia concinna (Willd.) DC. is a medicinal plant sourced mainly from Southeast Asia. The pods of Acacia concinna (A. concinna) are a potential candidate to treat or prevent obesity; however, these medicinal attributes have not been examined in detail. In this study, the anti-obesogenic compounds in A. concinna pods were investigated. Chromatographic separation of the pod extract guided by pancreatic lipase inhibitory activity led to the isolation of saponins. Decomposition analysis of the saponins revealed their chemical composition to be acacic acid, monoterpenes, and five types of sugars (glucose, xylose, rhamnose, quinovose, arabinose). The predicted structures of the saponins from decomposition analysis were confirmed by LC-MS analysis, showing that these saponins are mixture of various derivatives of monoterpenes and sugar units. These saponins inhibited pancreatic lipase activity strongly with an IC50 of 7.9μg/mL, and reduced lipid accumulation in 3T3-L1 adipocytes at 6.3μg/mL. The saponins also enhanced lipolysis of 3T3-L1 adipocytes at 3.1 or 6.3μg/mL by mediating the activity of protein kinase A and extracellular signal-regulated kinase pathways, suggesting that this mechanism is partly responsible for the observed reduction of lipid content in adipocytes. The results underline A. concinna as a potential source of the anti-obesogenic candidates for the future treatment and prevention of obesity.

Selected Monocyclic Monoterpenes and Their Derivatives as Effective Anticancer Therapeutic Agents.

Terpenes—a diverse group of secondary metabolites—constitute the largest class of natural products abundant in almost every plant species. The properties of concrete terpenes and essential oils have been intensively studied due to their widespread use in the pharmaceutical, food and cosmetics industries. Despite the popularity of these aromatic compounds, their derivatives, terpenoids, are still not comprehensively characterized despite exhibiting potent bioactive properties. This review aims to assess the anticancer properties of selected monoterpenes including carvone, carvacrol, perillyl alcohol, perillaldehyde, limonene, menthol and their derivatives while also evaluating potential applications as novel anticancer treatments. Special attention is paid to functional groups that improve the bioactivity of monoterpene molecules. This review also covers the therapeutic potential of deep eutectic solvents that contain monoterpene substances. Taken together, the literature supports the use of monoterpene derivatives in the development of new alternatives for disease treatment and prevention.

Catalytic Epoxidation of 3-Carene and Limonene with Aqueous Hydrogen Peroxide, and Selective Synthesis of α-Pinene Epoxide from Turpentine

The epoxidation of turpentine (technical α-pinene), 3-carene, and limonene with aqueous hydrogen peroxide was studied in a new catalytic system employing manganese sulfate, salicylic acid, sodium bicarbonate, and acetonitrile, as a polar solvent. The proposed approach makes it possible to carry out a “chemical separation” of turpentine components, yielding valuable individual derivatives of monoterpenes without the need to isolate individual monoterpene reagents. Specific methods have been developed for the production of α-pinene epoxide, 3-carene epoxide, limonene diepoxide, as well as for two related compounds: 3-carene-5-one and 3-carene-2,5-dione.

D-limonene from orange (Citrus Maxima) peel extraction as destructive agent of styrofoam waste

Styrofoam is widely used for food packaging because it has good weight, stability, and stiffness but it cannot be decomposed naturally by microorganisms. D-Limonene, one of the monoterpene derivatives, is an environmentally friendly styrofoam solvent. This monoterpene is the main component of essential oil that can be extracted from orange peel. The aim of this study is to destruct styrofoam wastes (foods packaging, electronics packaging, foam boards and cup noodles) using d-limonene from orange (Citrus Maxima) peel extraction by water distillation process. The orange peel after size reduction is extracted by water distillation process at 94°C for 7 hours to produce essential oils. It was used to destruct styrofoam waste at the different volume ratio (1:0:0; 1:0:3; 1:1:2; 1:2:1) of the essential oil mixture (essential oil : ethanol: water). The result of this study shows that styrofoam wastes can be destructed using d-limonene from orange (Citrus Maxima) peel extraction. D-limonene of essential oil from orange (Citrus Maxima) peel can be used as destructive agent of styrofoam waste. The fastest destruction time of styrofoam waste occurs at electronic packaging with essential oil mixture by volume ratio of 1:1:2.

LC-MS based identification of stylosin and tschimgine from fungal endophytes associated with Ferula ovina.

Objective(s): Ferula ovina is an Iranian medicinal plant. Tschimgine and stylosin are two of its major monoterpene derivatives. In this study, we proceeded to investigate some fungal endophytes from F. ovina that can produce plant secondary metabolites.Materials and Methods:The isolated endophytic fungi were fermented in potato dextrose broth (PDB) medium and their extracts were screened for the presence of the plant compounds by liquid chromatography-tandem mass spectrometry (LC-MS). Endophytes identification was performed by morphological and molecular methods. Three markers (ITS, LSU, and TEF1) were used for accurate molecular identification. Results:Forty isolates from 9 different genera of endophytic fungi were identified, of which two recently reported species of O. ferulica and Pithoascus persicus were able to produce tschimgine and stylosin. Conclusion:These fungi can be used as a substitute for the production of plant’s medicinal compounds independent of wild populations of the source plant.

Особенности накопления биологически активных веществ в растениях Elsholtzia stauntonii Benth., выращиваемых в предгорной зоне Крыма

Abstract. The purpose of the research was to study the quality of Elsholtzia stauntonii Benth. raw materials grown in the foothill zone of the Crimea. In the course of the research, we studied such indicators as the content of essential oil and other types of biologically active substances (BAS), which allow using elsholtzia as an essential oil, food, or medicinal raw materials. Research methods. Determination of the quality of E. stauntonii raw materials was carried out according to generally accepted methods. Results. Peculiarities of the accumulation of essential oil in various organs of E. stauntonii were determined. The variability of the mass fraction of essential oil, its component composition and BAS depending on the plant’s growth stage is shown. We found that the main oil-synthesizing organs of E. stauntonii are leaves and inflorescences. The largest amount of essential oil (1.82 %) was obtained from inflorescences. In the fractional composition of raw materials, they amounted to 45.6 %. The maximum amount of essential oil with the dominant components (rosefuran and rosefuran epoxide) accumulated in plants during the phase of mass flowering (1.48 % in terms of absolutely dry weight). The highest content of BAS, namely phenolic compounds, accumulated in the stage of active growth of vegetative and the formation of generative organs of plants (regrowth and bud formation); extractives – in the stage of regrowth. During two years of storage of air-dry raw materials, there is a loss of essential oil as a result of its evaporation (54.0 %) and a change in its component composition (an increase in monoterpene derivatives of furan by 26.6 % and a decrease in sesquiterpene hydrocarbons by 23.5 %). To store air-dry raw materials of E. stauntonii for more than two years is not, however, reasonable because of significant losses of essential oil. Scientific novelty. The quality of raw materials of E. stauntonii variety Rozovoe oblako, which was grown in the foothill zone of the Crimea, was studied for the first time. Raw materials and essential oil of E. stauntonii have a broad spectrum of biological activity and can be used in medicine, as well as in essential oil and food industries.

Prostanthera (Lamiaceae) as a 'Cradle of Incense': Chemophenetics of Rare Essential Oils from Both New and Forgotten Australian 'Mint Bush' Species.

The highly aromatic Australian mint bushes from the genus Prostanthera Labill. produce a high yield of essential oil on hydrodistillation. Together with its rich history, horticultural potential, iconic flowers, and aromatic leaves, it achieves high ornamental and culinary value. Species in the genus express highly diverse and chemically unique essential oils that demonstrate intra- and inter-specific patterns that have inspired taxonomic reinterpretation for over a hundred years. Previous studies have conveyed that phenoplastic expression of volatiles creates chemotypes within taxa, adding complexity to chemophenetic exploration. The current study chemically characterised essential oils from 64 highly aromatic specimens, representative of 25 taxa, giving yields as high as >2% g/g. The chemical profiles of essential oils are diverse, but generally include 1,8-cineole and signatory compounds such as sesquiterpene oxides, caryophyllene oxide, kessane and cis-dihydroagarofuran; sesquiterpene alcohols, globulol, epiglobulol, maaliol, prostantherol, spathulenol and ledol; and monoterpene derivatives of common scaffolds, borneol, bornyl acetate, bornanone, linalool and linalyl acetate. As in previous studies, analysis of chemical data confirms that the chemistry strongly agrees with taxonomic classifications. Importantly, as in classical taxonomy, the current chemical study complemented morphological analysis but conveys chemovariation, obscuring the taxonomic agreement. Nevertheless, variation within taxa may be due to environmental factors, meaning that cultivation of species in gardens will create different chemical profiles as compared to those published here.

Synthesis of a pyrrolidine derivative of a carvotacetone and monoterpenes for anti-methicillin-resistant Staphylococcus aureus and anti-cryptococcal properties

Monoterpene derivatives are of great biological relevance in the pharmaceutical industry. In the present study, pyrrolidine derivative of a carvotacetone, 3-O-benzylcarvotacetone (1), and selected monoterpenes (3-hydroxy-2-isopropyl-5-methyl-p-benzoquinone (3) and cis-piperitol (5)) were prepared to provide (R)-1-(4-(benzyloxy)-5-isopropyl-2-methylcyclohexa-1,3-dien-1-yl)-pyrrolidine (2), 2-isopropyl-5-methyl-3,6-dioxocyclohexa-1,4-dien-1-yl acetate (4), cis-3-hydroxypiperitone (6) and carvacrol (7). Structure of 2 was determined based on NMR and HRMS spectral data. Compound 4 exhibited activity against fungi Cryptococcus neoformans with an IC50 value of < 0.8 µg/mL. In addition, this compound 4 had an IC50 value of 14.97 µg/mL against methicillin resistant Staphylococcus aureus bacteria. Previous to the current study, both compound 6 and 7 had been reported to have anti-microbial and anti-fungal activities.

TMPE Derived from Saffron Natural Monoterpene as Cytotoxic and Multidrug Resistance Reversing Agent in Colon Cancer Cells.

Terpenes constitute one of the largest groups of natural products. They exhibit a wide range of biological activities including antioxidant, anticancer, and drug resistance modulating properties. Saffron extract and its terpene constituents have been demonstrated to be cytotoxic against various types of cancer cells, including breast, liver, lung, pancreatic, and colorectal cancer. In the present work, we have studied anticancer properties of TMPE, a newly synthesized monoterpene derivative of β-cyclocitral—the main volatile produced by the stigmas of unripe crocuses. TMPE presented selective cytotoxic activity to doxorubicin-resistant colon cancer cells and was identified to be an effective MDR modulator in doxorubicin-resistant cancer cells. Synergy between this derivative and doxorubicin was observed. Most probably, TMPE inhibited transport activity of ABCB1 protein without affecting its expression level. Analysis of TMPE physicochemical parameters suggested it was not likely to be transported by ABCB1. Molecular modeling showed TMPE being more reactive molecule than the parental compound—β-cyclocitral. Analysis of electrostatic potential maps of both compounds prompted us to hypothesize that reduced reactivity as well as susceptibility to electrophilic attack were related to the lower general toxicity of β-cyclocitral. All of the above pointed to TMPE as an interesting candidate molecule for MDR reversal in cancer cells.

Metabolite Profiling and Transcriptome Analysis Revealed the Chemical Contributions of Tea Trichomes to Tea Flavors and Tea Plant Defenses.

Tea trichomes contain special flavor-determining metabolites; however, little is known about how and why tea trichomes produce them. Integrated metabolite and transcriptome profiling on tea trichomes in comparison with that on leaves showed that trichomes contribute to tea plant defense and tea flavor and nutritional quality. These unicellular, nonglandular, and unbranched tea trichomes produce a wide array of tea characteristic metabolites, such as UV-protective flavonoids, insect-toxic caffeine, herbivore-defensive volatiles, and theanine, as evidenced by the expression of whole sets of genes involved in different metabolic pathways. Both dry and fresh trichomes contain several volatiles and flavonols that were not found or at much low levels in trichome-removed leaves, including benzoic acid derivatives, lipid oxidation derivatives, and monoterpene derivatives. Trichomes also specifically expressed many disease signaling genes and various antiherbivore or antiabiotic peptides. Trichomes are one of the domestication traits in tea plants. Tea trichomes contribute to tea plant defenses and tea flavors.

Metabolic Engineering of the Native Monoterpene Pathway in Spearmint for Production of Heterologous Monoterpenes Reveals Complex Metabolism and Pathway Interactions.

Spearmint produces and stores large amounts of monoterpenes, mainly limonene and carvone, in glandular trichomes and is the major natural source of these compounds. Towards producing heterologous monoterpenes in spearmint, we first reduced the flux into the native limonene pathway by knocking down the expression of limonene synthase (MsLS) by RNAi method. The MsLS RNAi lines exhibited a huge reduction in the synthesis of limonene and carvone. Detailed GC-MS and LC-MS analysis revealed that MsLS RNAi plants also showed an increase in sesquiterpene, phytosterols, fatty acids, flavonoids, and phenolic metabolites, suggesting an interaction between the MEP, MVA shikimate and fatty acid pathways in spearmint. Three different heterologous monoterpene synthases namely, linalool synthase and myrcene synthase from Picea abies and geraniol synthase from Cananga odorata were cloned and introduced independently into the MsLS RNAi mutant background. The expression of these heterologous terpene synthases resulted mainly in production of monoterpene derivatives. Of all the introduced monoterpenes geraniol showed the maximum number of derivatives. Our results provide new insights into MEP pathway interactions and regulation and reveals the existence of mechanisms for complex metabolism of monoterpenes in spearmint.

(+)-Limonene 1,2-Epoxide-Loaded SLNs: Evaluation of Drug Release, Antioxidant Activity, and Cytotoxicity in an HaCaT Cell Line.

In this work, we developed a solid lipid nanoparticle (SLN) formulation with (+)-limonene 1,2-epoxide and glycerol monostearate (Lim-SLNs), stabilized with Poloxamer® 188 in aqueous dispersion to modify the release profile of the loaded monoterpene derivative. We also evaluated the role of SLNs in lipid peroxidation and cytotoxicity in a spontaneously transformed aneuploid immortal keratinocyte cell line from adult human skin (the HaCaT cell line). For the cell viability assay, the colorimetric 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used. Lim-SLNs with a loading capacity and encapsulation efficiency of 0.39% and 63%, respectively, were produced by high pressure homogenization. A mean particle size of 194 ± 3.4 nm and polydispersity index of 0.244 were recorded for the loaded Lim-SLNs, as compared to 203 ± 1.5 nm (PI 0.213) for the non-loaded (blank) SLNs. The loading of the monoterpene derivative into glycerol monostearate SLNs fitted into the zero-order kinetics, and ameliorated both lipid peroxidation and cytotoxicity in a keratinocyte cell line. A promising formulation for antioxidant and anti-tumoral activities is here proposed.

Asymmetric Synthesis of Fluorinated Monoterpenic Alkaloid Derivatives from Chiral Fluoroalkyl Aldimines via the Pauson‐Khand Reaction

AbstractEnantioenriched fluorinated monoterpenic alkaloid analogues were synthesised, employing a strategy based on the previously undescribed diastereoselective propargylation of fluorinated tert‐butanesulfinyl imines, and subsequent Pauson‐Khand reaction of resulting enyne derivatives, carried out both stoichiometrically and catalytically. The Pauson‐Khand reaction tolerated both substituted alkenes and alkynes, and took place in good yields and diastereoselectivities, even when applied to a gram‐scale synthesis.magnified image