Unraveling the effective inhibition of α-terpinol and terpene-4-ol against Aspergillus carbonarius: Antifungal mechanism, ochratoxin A biosynthesis inhibition and degradation perspectives.

Aspergillus carbonarius, a common food-contaminating fungus, produces ochratoxin A (OTA) and poses a risk to human health. This study aimed to assess the inhibitory activity of tea tree essential oil and its main components, Terpene-4-ol (T4), α-terpineol (αS), and 3-carene (3C) against A. carbonarius. The study showed αS and T4 were the main antifungal components of tea tree essential oil, which primarily inhibit A. carbonarius growth through cell membrane disruption, reducing antioxidant enzyme activities (catalase, peroxidase, superoxide dismutase) and interrupting the tricarboxylic acid cycle. Furthermore, αS and T4 interacted with enzymes related to OTA biosynthesis. Molecular docking and molecular dynamics show that they bound mainly to P450 with a minimum binding energy of -7.232 kcal/mol, we infered that blocking the synthesis of OTA precursor OTß. Our hypothesis was preliminarily verified by the detection of key substances in the OTA synthesis pathway. The results of UHPLC-QTOF-MS2 analysis demonstrated that T4 achieved a degradation rate of 43 % for OTA, while αS reached 29.6 %, resulting in final breakdown products such as OTα and phenylalanine. These results indicated that α-terpinol and Terpene-4-ol have the potential to be used as naturally safe and efficient preservatives or active packaging to prevent OTA contamination.

Comparative Analysis of Hydrosol Volatile Components of Citrus × Aurantium 'Daidai' and Citrus × Aurantium L. Dried Buds with Different Extraction Processes Using Headspace-Solid-Phase Microextraction with Gas Chromatography-Mass Spectrometry.

This work used headspace solid-phase microextraction with gas chromatography-mass spectrometry (HS-SPME-GC-MS) to analyze the volatile components of hydrosols of Citrus × aurantium 'Daidai' and Citrus × aurantium L. dried buds (CAVAs and CADBs) by immersion and ultrasound-microwave synergistic-assisted steam distillation. The results show that a total of 106 volatiles were detected in hydrosols, mainly alcohols, alkenes, and esters, and the high content components of hydrosols were linalool, α-terpineol, and trans-geraniol. In terms of variety, the total and unique components of CAVA hydrosols were much higher than those of CADB hydrosols; the relative contents of 13 components of CAVA hydrosols were greater than those of CADB hydrosols, with geranyl acetate up to 15-fold; all hydrosols had a citrus, floral, and woody aroma. From the pretreatment, more volatile components were retained in the immersion; the relative contents of linalool and α-terpineol were increased by the ultrasound-microwave procedure; and the ultrasound-microwave procedure was favorable for the stimulation of the aroma of CAVA hydrosols, but it diminished the aroma of the CADB hydrosols. This study provides theoretical support for in-depth exploration based on the medicine food homology properties of CAVA and for improving the utilization rate of waste resources.

Transcription Factor PdTP1 Regulates the Biotransformation of Limonene to α-Terpineol and the Growth of Penicillium digitatum.

α-Terpineol, an alcoholic monoterpene with lilac-like aroma, possesses diverse biological activities and has found applications in the food, pharmaceutical, cosmetic, and agricultural industries. Our previous studies indicated that gene PdTP1 was highly expressed in Penicillium digitatum DSM 62840 during the biotransformation of limonene to α-terpineol, while its actual biological functions are not fully understood. Here, PdTP1 was functionally characterized with bioinformatics analysis, subcellular localization, transcriptional activation activity, overexpression, and RNA interference (RNAi) silencing and RNA-seq analysis. Results showed that PdTP1 protein contained a GAL4-like Zn2Cys6 DNA-binding domain and a fungal_trans domain, was located in the nucleus and cell membrane and presented transcriptional activation effect, suggesting that PdTP1 encoded a Zn2Cys6 type transcription factor. Overexpression of PdTP1 in P. digitatum promoted limonene biotransformation and increased α-terpineol production, and opposite results were observed after the silencing of PdTP1. Moreover, transcription factor PdTP1 was found to affect the growth of P. digitatum and participate in ionic stress and oxidative stress responses. RNA-seq data revealed that altering the PdTP1 expression influenced the expression of some genes related to terpene metabolism or biosynthesis, fungal growth, and stress responses. In summary, PdTP1, which encoded a Zn2Cys6 transcription factor, played important roles in improving the production of α-terpineol from limonene and regulating fungal growth and environmental stress responses.

A novel mutation in non-constitutive lycopene beta cyclase (CstLcyB2a) from Crocus sativus modulates carotenoid/apocarotenoid content, biomass and stress tolerance in plants.

MAIN CONCLUSION: Mutation at A126 in lycopene-ß-cyclase of Crocus (CstLcyB2a) sterically hinders its binding of δ-carotene without affecting lycopene binding, thereby diverting metabolic flux towards ß-carotene and apocarotenoid biosynthesis. Crocus sativus, commonly known as saffron, has emerged as an important crop for research because of its ability to synthesize unique apocarotenoids such as crocin, picrocrocin and safranal. Metabolic engineering of the carotenoid pathway can prove a beneficial strategy for enhancing the quality of saffron and making it resilient to changing climatic conditions. Here, we demonstrate that introducing a novel mutation at A126 in stigma-specific lycopene-ß-cyclase of Crocus (CstLcyB2a) sterically hinders its binding of δ-carotene, but does not affect lycopene binding, thereby diverting metabolic flux towards ß-carotene formation. Thus, A126L-CstLcyB2a expression in lycopene-accumulating bacterial strains resulted in enhanced production of ß-carotene. Transient expression of A126L-CstLcyB2a in C. sativus stigmas enhanced biosynthesis of crocin. Its stable expression in Nicotiana tabacum enhanced ß-branch carotenoids and phyto-hormones such as abscisic acid (ABA) and gibberellic acids (GA's). N. tabacum transgenic lines showed better growth performance and photosynthetic parameters including maximum quantum efficiency (Fv/Fm) and light-saturated capacity of linear electron transport. Exogenous application of hormones and their inhibitors demonstrated that a higher ratio of GA4/ABA has positive effects on biomass of wild-type and transgenic plants. Thus, these findings provide a platform for the development of new-generation crops with improved productivity, quality and stress tolerance.

Thiazolidinone-linked-1,2,3-triazoles with (R)-Carvone as new potential anticancer agents.

Aim: This study explores the cytotoxic and apoptotic effects of novel thiazolidinone-1,2,3-triazole hybrids on HT-1080, A-549, and MDA-MB-231 cancer cell lines.Methods & results: The synthesized compounds underwent comprehensive characterization (NMR and HRMS) to confirm their structures and purity. Subsequent anticancer activity screening across diverse cancer cell lines revealed promising antitumor potential notably, compounds 6f and 6g. Mechanistic investigations unveiled that compound 6f triggers apoptosis through the caspase-3/7 pathway. In terms of in silico studies, the compound 6f was identified as a potent inhibitor of caspase-3 and caspase-7.Conclusion: The present study underscores the therapeutic potential of thiazolidinone-1,2,3-triazole hybrids against certain cancer cells. These findings highlight a promising avenue for the development of cancer treatment strategies utilizing these (R)-Carvone-based derivatives.

[Box: see text].

Evaluation of Different Drying Treatments with Respect to Essential Oil Components, Phenolic and Flavonoid Compounds, and Antioxidant Capacity of Ajowan (Trachyspermum ammi L.).

Ajowan (Trachyspermum ammi L.) is considered a valuable spice and medicinal herb. In this study, the essential oil content and composition of the aerial parts of ajowan were investigated under different drying treatments (sun, shade, oven at 45 °C, oven at 65 °C, microwave, and freeze drying). Moreover, the phenolic content, flavonoid content, and antioxidant capacity of samples were also assessed. Fresh samples produced the highest essential oil content (1.05%), followed by those treated under sun (0.7%) and shade drying (0.95%). Based on gas chromatography-mass spectrometry (GC-MS), thirty compounds were determined in which thymol (34.84-83.1%), carvacrol (0.15-32.36%), p-cymene (0.09-13.66%), and γ-terpinene (3.12-22.58%) were the most abundant. Among the drying methods, freeze drying revealed the highest thymol content, followed by drying in a 45 °C oven. The highest TPC (total phenolic content) and TFC (total flavonoid content) were obtained in the fresh sample (38.23 mg TAE g-1 dry weight (DW)) and in the sample oven-dried at 45 °C (7.3 mg QE g-1 DW), respectively. Based on the HPLC results, caffeic acid (18.04-21.32 mg/100 gDW) and ferulic acid (13.102-19.436 mg/100 g DW) were the most abundant phenolic acids, while among flavonoids, rutin constituted the highest amount (10.26-19.88 mg/100 gDW). Overall, freeze drying was the most promising method of drying for preserving the phenolic (TPC) and flavonoid (TFC) compounds and oil components.

Antihyperalgesic effect of γ-terpinene complexed in ß-cyclodextrin on neuropathic pain model induced by tumor cells.

Neuropathic pain is a high-intensity pain that can be caused by compression, transection, injury, nerve infiltration and drug treatment of cancer. Furthermore, drug therapy has low clinical efficacy, many adverse effects and remission of painful symptoms. In this way, natural products derived from plants constitute a promising therapeutic alternative. Therefore, the aim of this study was to evaluate the antihyperalgesic effect of γ-terpinene (γ-TPN) e γ-terpinene in ß-cyclodextrin inclusion complexes (TPN/CD) on neuropathic pain induced by tumor cells. Complexation extended the effect time for another 5 h and daily treatment for six days with γ-TPN (50 mg/kg, p.o.) and γ-TPN/ß-CD (50 mg/kg, p.o.) significantly reduced (p < 0.001) the mechanical hyperalgesia induced by the administration of 2x106 sarcoma cells 180 in the around the sciatic nerve. In addition, the Grip and Rota-rod techniques demonstrated that there was no interference on the muscle strength and motor coordination of the animals, suggesting that the compound under study does not have central nervous system depressant effects at the doses used. Molecular docking studies demonstrate favorable binding energies between γ-TPN and ß-CD, and alpha-2 adrenergic, glutamatergic, opioid and cholinergic receptors. Thus, this study demonstrates the potential of terpinene complexation in controlling neuropathic pain induced by tumor cells.

The aroma profiles of dried gonggans: Characterization of volatile compounds in oven-dried and freeze-dried gonggan.

Dehydration is an effective method for the long-term storage and aroma retention of gonggan (Citrus sinensis Osb. 'Deqing Gonggan'), which is a Chinese variety of citrus, with unique and characteristic floral, fruity, and citrus flavors. However, the aroma profiles of gonggans prepared using oven- and freeze-drying, the most widely-used drying methods, remain unclear. In this study, a total of 911 volatile organic compounds (VOCs) were detected in dried gonggan. These were primarily composed of alcohols (7.69%), aldehydes (7.03%), esters (15.38%), ketones (7.58%), and terpenoids (23.19%). A total of 67 odorants contributed significantly to the overall aroma of dried gonggans, with the major odor qualities being detected as green, citrus, fruity, floral, and sweet. These were mainly attributed to the presence of aldehydes, esters, and terpenoids. Freeze-drying was more effective in maintaining the unique citrus and mandarin-like aromas attributed to compounds such as limonene, citrial, ß-myrcene, ß-pinene, and γ-terpinene. Moreover, (E,E)-2,4-decadienal had the highest relative odor activity value (rOAV) in freeze-dried gonggans, followed by (E)-2-nonenal, furaneol, (E, E)-2, 4-nonadienal, and E-2-undecenal. Oven-drying promoted the accumulation of terpenes such as octatriene, trans-ß-ocimene, cyclohexanone, copaene, and ɑ-irone, imparting a soft aroma of flowers, fruits, and sweet. Increasing the temperature led to an increase in existing VOCs or the generation of new VOCs through phenylpropanoid, terpenoid, and fatty acid metabolism. The findings of this study offer insights into an optimized procedure for producing high-quality dried gonggans. These insights can be valuable for the fruit-drying industry, particularly for enhancing the quality of dried fruits.

New Polymeric Hydrogels with Cannabidiol and α-Terpineol as Potential Materials for Skin Regeneration-Synthesis and Physicochemical and Biological Characterization.

Dermatology and cosmetology currently prioritize healthy, youthful-looking skin. As a result, research is being conducted worldwide to uncover natural substances and carriers that allow for controlled release, which could aid in the battle against a variety of skin illnesses and slow the aging process. This study examined the biological and physicochemical features of novel hydrogels containing cannabidiol (CBD) and α-terpineol (TER). The hydrogels were obtained from ε-caprolactone (CL) and poly(ethylene glycol) (PEG) copolymers, diethylene glycol (DEG), poly(tetrahydrofuran) (PTHF), 1,6-diisocyanatohexane (HDI), and chitosan (CHT) components, whereas the biodegradable oligomers were synthesized using the enzyme ring-opening polymerization (e-ROP) method. The in vitro release rate of the active compounds from the hydrogels was characterized by mainly first-order kinetics, without a "burst release". The antimicrobial, anti-inflammatory, cytotoxic, antioxidant, and anti-aging qualities of the designed drug delivery systems (DDSs) were evaluated. The findings indicate that the hydrogel carriers that were developed have the ability to scavenge free radicals and impact the activity of antioxidant enzymes while avoiding any negative effects on keratinocytes and fibroblasts. Furthermore, they have anti-inflammatory qualities by impeding protein denaturation as well as the activity of proteinase and lipoxygenase. Additionally, their ability to reduce the multiplication of pathogenic bacteria and inhibit the activity of collagenase and elastase has been demonstrated. Thus, the developed hydrogel carriers may be effective systems for the controlled delivery of CBD, which may become a valuable tool for cosmetologists and dermatologists.

Effects of aluminum (Al) stress on the isoprenoid metabolism of two Citrus species differing in Al-tolerance.

Isoprenoid metabolism and its derivatives took part in photosynthesis, growth regulation, signal transduction, and plant defense to biotic and abiotic stresses. However, how aluminum (Al) stress affects the isoprenoid metabolism and whether isoprenoid metabolism plays a vital role in the Citrus plants in coping with Al stress remain unclear. In this study, we reported that Al-treatment-induced alternation in the volatilization rate of monoterpenes (α-pinene, ß-pinene, limonene, α-terpinene, γ-terpinene and 3-carene) and isoprene were different between Citrus sinensis (Al-tolerant) and C. grandis (Al-sensitive) leaves. The Al-induced decrease of CO2 assimilation, maximum quantum yield of primary PSII photochemistry (Fv/Fm), the lower contents of glucose and starch, and the lowered activities of enzymes involved in the mevalonic acid (MVA) pathway and 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway might account for the different volatilization rate of isoprenoids. Furthermore, the altered transcript levels of genes related to isoprenoid precursors and/or derivatives metabolism, such as geranyl diphosphate (GPP) synthase (GPPS) in GPP biosynthesis, geranylgeranyl diphosphate synthase (GGPPS), chlorophyll synthase (CHS) and GGPP reductase (GGPPR) in chlorophyll biosynthesis, limonene synthase (LS) and α-pinene synthase (APS) in limonene and α-pinene synthesis, respectively, might be responsible for the different contents of corresponding products in C. grandis and C. sinensis. Our data suggested that isoprenoid metabolism was involved in Al tolerance response in Citrus, and the alternation of some branches of isoprenoid metabolism could confer different Al-tolerance to Citrus species.

Bioactivities and Synergistic Effect of Elsholtzia ciliata Essential Oil and Its Main Components against Lasioderma serricorne.

Investigations have shown that storage bugs seriously harm grains during storage. In the interim, essential oils (EOs) have been proven to be a good botanical pesticide. The anti-Lasioderma serricorne properties of Elsholtzia ciliata essential oil, which was obtained by steam distillation, were evaluated using DL-limonene, carvone, and their two optical isomer components using contact, repelling, and fumigation techniques. Simultaneously, the fumigation, contact, and repellent activities of carvone and its two optical isomers mixed with DL-limonene against L. serruricorne were evaluated. The results showed that E. ciliata, its main components (R-carvone, DL-limonene), and S-carvone exhibited both fumigations (LC50 = 14.47, 4.42, 20.9 and 3.78 mg/L) and contact (LD50 = 7.31, 4.03, 28.62 and 5.63 µg/adult) activity against L.serricorne. A binary mixture (1:1) of R-carvone and DL-limonene displayed an obvious synergistic effect. A binary mixture (1:1) of carvone and its two optical isomers exhibited an obvious synergistic effect, too. Furthermore, the repellent activity of the EO, carvone, and its two optical isomers, DL-limonene, and a combination of them varied. To stop insect damage during storage, E. ciliata and its components can be utilized as bio-insecticides.

Chemical Characterization of the Essential Oil Compositions of Mentha spicata and M. longifolia ssp. cyprica from the Mediterranean Basin and Multivariate Statistical Analyses.

This present study aims to characterize the essential oil compositions of the aerial parts of M. spicata L. and endemic M. longifolia ssp. cyprica (Heinr. Braun) Harley by using GC-FID and GC/MS analyses simultaneously. In addition, it aims to perform multivariate statistical analysis by comparing with the existing literature, emphasizing the literature published within the last two decades, conducted on both species growing within the Mediterranean Basin. The major essential oil components of M. spicata were determined as carvone (67.8%) and limonene (10.6%), while the major compounds of M. longifolia ssp. cyprica essential oil were pulegone (64.8%) and 1,8-cineole (10.0%). As a result of statistical analysis, three clades were determined for M. spicata: a carvone-rich chemotype, a carvone/trans-carveol chemotype, and a pulegone/menthone chemotype, with the present study result belonging to the carvone-rich chemotype. Carvone was a primary determinant of chemotype, along with menthone, pulegone, and trans-carveol. In M. longifolia, the primary determinants of chemotype were identified as pulegone and menthone, with three chemotype clades being pulegone-rich, combined menthone/pulegone, and combined menthone/pulegone with caryophyllene enrichment. The primary determinants of chemotype were menthone, pulegone, and caryophyllene. The present study result belongs to pulegone-rich chemotype.

An Effective and Promising Strategy for Plant Protection: Synthesis of L-Carvone-Based Thiazolinone-Hydrazone/Nanochitosan Complexes with Antifungal Activity and Sustained Releasing Performance.

The development of novel natural product-derived nano-pesticide systems with loading capacity and sustained releasing performance of bioactive compounds is considered an effective and promising plant protection strategy. In this work, 25 L-carvone-based thiazolinone-hydrazone compounds 4a~4y were synthesized by the multi-step modification of L-carvone and structurally confirmed. Compound 4h was found to show favorable and broad-spectrum antifungal activity through the in vitro antifungal activity evaluation of compounds 4a~4y against eight phytopathogenic fungi. Thus, it could serve as a leading compound for new antifungal agents in agriculture. Moreover, the L-carvone-based nanochitosan carrier 7 bearing the 1,3,4-thiadiazole-amide group was rationally designed for the loading and sustained releasing applications of compound 4h, synthesized, and characterized. It was proven that carrier 7 had good thermal stability below 200 °C, dispersed well in the aqueous phase to form numerous nanoparticles with a size of~20 nm, and exhibited an unconsolidated and multi-aperture micro-structure. Finally, L-carvone-based thiazolinone-hydrazone/nanochitosan complexes were fabricated and investigated for their sustained releasing behaviors. Among them, complex 7/4h-2 with a well-distributed, compact, and columnar micro-structure displayed the highest encapsulation efficiency and desirable sustained releasing property for compound 4h and thus showed great potential as an antifungal nano-pesticide for further studies.

Neuroprotective Effects of [Formula: see text]-Terpinene in Rats with Acute Cerebral Ischemia: Modulation of Inflammation, Apoptosis, and Oxidation.

The study aimed to assess 𝛾-Terpinene's (𝛾-TER) neuroprotective potential in acute cerebral ischemia, characterized by reduced cerebral blood flow in rats. Middle cerebral artery occlusion (MCAO), a standard method for inducing cerebral ischemia, was employed in male Wistar rats. 𝛾-TER at varying doses (5, 10, and 15 mg/kg) were intraperitoneally administered during reperfusion onset. Neurological outcomes, cerebral infarct size, edema, and enzymatic activities (SOD, GPx, and catalase) in the brain were evaluated using diverse techniques. The study examined gene expression and pathways associated with neuroinflammation and apoptosis using Cytoscape software, identifying the top 10 genes involved. Pro-inflammatory and pro-apoptotic factors were assessed through real-time PCR and ELISA, while apoptotic cell rates were measured using the TUNEL and Flow cytometry assay. Immunohistochemistry assessed apoptosis-related proteins like Bax and bcl-2 in the ischemic area. 𝛾-TER, particularly at doses of 10 and 15 mg/kg, significantly reduced neurological deficits and cerebral infarction size. The 15 mg/kg dose mitigated TNF-α, IL-1ß, Bax, and caspase-3 gene and protein levels in the cortex, hippocampus, and striatum compared to controls. Furthermore, Bcl-2 levels increased in these regions. 𝛾-TER show cased neuroprotective effects by suppressing inflammation, apoptosis, and oxidation. In conclusion, 𝛾-TER, possessing natural anti-inflammatory and anti-apoptotic properties, shields the brain against ischemic damage by reducing infarction, edema, oxidative stress, and inflammation. It modulates the expression of crucial genes and proteins associated with apoptosis in diverse brain regions. These findings position 𝛾-TER as a potential therapeutic agent for ischemic stroke.

Multi-targeted effects of D-carvone against Non-Small Cell Lung Cancer (NSCLC): A network pharmacology-based study.

Non-small cell lung cancer (NSCLC) is a complex malignancy with a high degree of heterogeneity, representing approximately 85% of all lung cancer cases. The treatment landscape for NSCLC has been revolutionised by incorporating targeted and immunotherapies; however, novel therapeutic modalities are consistently needed to enhance the treatment outcomes. Indeed, alternative anti-cancer therapies involving natural products have drawn the attention of clinicians and scientists owing to their remarkable chemopreventive potential, often displaying minimal toxicity. D-carvone (CN) is one such natural product that has exhibited numerous promising therapeutic benefits, yet its efficacy against NSCLC remains enigmatic. In the present study, network pharmacological studies and molecular docking in conjunction with in-vitro validation were used to elucidate the underlying mechanism of action of CN comprehensively. Different databases revealed a total of 77 putative anti-NSCLC targets of CN. The identified core targets were utilised to construct a "Compound- Target- Disease" network by Cytoscape (v3.9.0). Further analysis identified 5 core/ hub targets of CN including JAK2, ERK1, ESR1, GSK3B and HSP90AA1. Molecular docking indicated a strong binding interaction of the compound with these core targets. Also, Gene Ontology and KEGG analysis validated the involvement of multiple biological processes. Additionally, CN significantly inhibited cell proliferation, clonogenicity, and wound healing potential while promoting apoptosis in a dose-dependent manner in H1299 and A549 cell lines as examined by flow cytometry, morphological assessment, and western blotting. In conclusion, this study delineates the therapeutic effects of CN on NSCLC, thus highlighting CN as a putative drug candidate for further analysis.

Volatile compositions and glandular trichomes of Zataria multiflora in different phenological stages under normal and drought stress conditions.

BACKGROUND: Zataria multiflora Boiss. is a medicinal and aromatic plant from the Lamiaceae family. It is extensively used in Iranian traditional medicine, mostly as a replacement for Thyme species. This study was focused on the analysis of chemical composition and the distribution and types of trichomes of Z. multiflora grown under different conditions. Equilibrium headspace analysis in combination with GC-FID-MS was used to identify volatile compounds released by aerial parts of Z. multiflora in development stages of 50 and 100% flowering under normal and drought-stress conditions. RESULTS: The main constituents were p-cymene (20.06-27.40%), γ-terpinene (12.44-16.93%), and α-pinene (6.91-16.58%) and thymol (8.52-9.99%). The highest content of p-cymene (27.40%) and thymol (9.99%) was observed in the 50% flowering stage at the 90% field capacity, while the maximum γ-terpinene (16.93%) content was recorded in the 100% flowering stage under normal conditions. Using the SEM method, it was found that peltate glandular and non-glandular trichomes are distributed on the surface of the leaf, stem, and outer side of the calyx. However, capitate trichomes only are detected on the stem and calyx in the 100% flowering and beginning of blooming stages, respectively. The type and structure of trichomes do not vary in different development stages, but they differ in density. The highest number of leaf peltate glandular trichomes was observed in the vegetative and beginning of blooming stages at 50% and 90% field capacity, respectively. Non-glandular trichomes of the stem were observed with high density in both normal and stress conditions, which are more densely in 90% field capacity. CONCLUSIONS: Since this plant has strong potential to be used in the food and pharmacological industries, this study provides valuable information for its cultivation and harvesting at specific phenological stages, depending on desired compounds and their concentrations.

Comparison of Approaches for Authentication of Commercial Terpinen-4-ol-type Tea Tree Oils Using Chiral GC/MS.

A global demand for tea tree oil (TTO) has resulted in increased adulteration in commercial products. In this study, we use a novel enantiomeric gas chromatography mass spectrometry method for chiral analysis of key terpenes ((±)-terpinen-4-ol, (±)-α-terpineol, and (±)-limonene) and quantification of components present at >0.01% to test different methods of identifying adulterated TTO. Data from authentic Australian (n = 88) and oxidized (n = 12) TTO samples of known provenance were consistent with recommended ranges in ISO 4730:2017 and previously published enantiomeric ratios, with p-cymene identified as the major marker of TTO oxidation. The 15 ISO 4730:2017 constituents comprised between 84.5 and 89.8% of the total ion chromatogram (TIC) peak area. An additional 53 peaks were detected in all samples (7.3-11.0% of TIC peak area), while an additional 43 peaks were detected in between 0 and 99% (0.15-2.0% of the TIC peak area). Analysis of nine commercial samples demonstrated that comparison to the ISO 4730:2017 standard does not always identify adulterated TTO samples. While statistical analysis of minor components in TTO did identify two commercial samples that differed from authentic TTO, the (+)-enantiomer percentages for limonene, terpinen-4-ol, and α-terpineol provided clearer evidence that these samples were adulterated. Thus, straightforward identification of unadulterated and unoxidized TTO could be based on analysis of appropriate enantiomeric ratios and quantitation of the p-cymene percentage.

Total Synthesis of a TNBC-Selective Cytotoxic Bromo Nor-eremophilane, PC-A, and Its Preliminary Structure-Activity Relationships.

PC-A (1), a bromo nor-eremophilane, showed selective antiproliferative activity against a triple-negative breast cancer (TNBC) cell line. This unique activity prompted us to establish a total synthesis to facilitate a structure-activity relationship (SAR) study and selectivity optimization. An enantioselective first total synthesis of 1 was achieved starting from (R)-carvone through a side chain extension with a Mukaiyama aldol reaction and decalin construction. The synthesized decalin derivatives and debromo PC-A (2) were evaluated for antiproliferative activity against five human tumor cell lines, including TNBC, to assess preliminary SAR correlations.

Eucalyptus Oils Phytochemical Composition in Correlation with Their Newly Explored Anti-SARS-CoV-2 Potential: in Vitro and in Silico Approaches.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the latest arisen contagious respiratory pathogen related to the global outbreak of atypical pneumonia pandemic (COVID-19). The essential oils (EOs) of Eucalyptus camaldulensis, E. ficifolia F. Muell., E. citriodora Hook, E. globulus Labill, E. sideroxylon Cunn. ex Woolls, and E. torquata Luehm. were investigated for its antiviral activity against SARS-CoV-2. The EOs phytochemical composition was determined using GC/MS analysis. Correlation with the explored antiviral activity was also studied using multi-variate data analysis and Pearson's correlation. The antiviral MTT and cytopathic effect inhibition assays revealed very potent and promising anti SARS-CoV-2 potential for E. citriodora EO (IC50 = 0.00019 µg/mL and SI = 26.27). The multivariate analysis revealed α-pinene, α-terpinyl acetate, globulol, γ -terpinene, and pinocarvone were the main biomarkers for E. citriodora oil. Pearson's correlation revealed that globulol is the top positively correlated compound in E. citriodora oil to its newly explored potent anti SARS-CoV-2 potential. A molecular simulation was performed on globulol via docking in the main active sites of both SARS-CoV-2 viral main protease (Mpro) and spike protein (S). In silico predictive ADMET study was also developed to investigate the pharmacokinetic profile and predict globulol toxicity. The obtained in silico, in vitro and Pearson's correlation results were aligned showing promising SARS-CoV-2 inhibitory activity of E. citriodora and globulol. This study is a first record for E. citriodora EO as a novel lead exhibiting potent in vitro, and in silico anti SARS-CoV-2 potential and suggesting its component globulol as a promising candidate for further extensive in silico, in vitro and in vivo anti-COVID studies.