Search Results (33)

Background: Gibberellins (GAs) are a family of tetracyclic ent-kaurenoid diterpenes found widely in several commonly used plants. Besides agricultural applications, gibberellins play an important role in the synthesis of bioactive compounds, especially those with antiproliferative and antibacterial activity. Methods: A series of gibberellic acid-based 2,4-diaminopyrimidines was designed and synthesized from commercially available gibberellic acid. The antimicrobial activity of the prepared compounds was also explored in B. subtilis, S. aureus, E. coli, and P. aeruginosa bacteria, as well as in C. krusei and C. albicans fungi. Results: The treatment of gibberellic acid with hydrochloric acid under reflux conditions resulted in aromatization followed by rearrangement to form allo-gibberic acid. The key intermediate azido alcohol was prepared according to the literature methods. The second key intermediate azidotriol was synthesized by the stereoselective dihydroxylation of the allylic function by the osmium (VIII)-tetroxide/NMO system. Starting from azide intermediates, click reactions were also carried out with 4-monoamino- and 2,4-diaminopyrimidines functionalized with the N-propargyl group. The new chimeric compounds, coupled with gibberellins thus obtained, were characterized by 1D- and 2D-NMR techniques and HRMS measurements. While the 4-monoamino-substituted derivatives exhibited only weak antibacterial activity, they demonstrated significant antifungal effectiveness against C. krusei. In general, 5-chloro-substituted pyrimidine derivatives displayed more consistent biological activities compared to their 5-fluoro counterparts, with the exception of one derivative, which showed acceptable activity against both C. krusei and C. albicans. The two derivatives featuring 5-chloro and 2-((4-(trifluoromethyl)phenyl)amino substituents proved to be highly effective against P. aeruginosa, making them promising candidates for further research. Aiming to elucidate the molecular interactions between the active compounds and their potential targets, molecular docking studies were conducted using AutoDock Vina 1.1.2. involving the most active compounds against P. aeruginosa.Conclusions: The biological effects of 2-monoamino or 2,4-diamino substitution as well as the effect of chloro or fluoro substitution at position 5 of the pyrimidine ring combined with the allo-gibberic acid moiety were determined. Compounds with selective antibacterial activity against P. aeruginosa as well as selective antifungal activity against C. krusei and C. albicans fungi were identified. Full article

Background: Phytol is a diterpene from the long-chain unsaturated acyclic alcohols, known for its diverse biological effects, including antimicrobial and anti-inflammatory activities. Present in essential oils, phytol is a promising candidate for various applications in the pharmaceutical and biotechnological sectors. This study aimed to evaluate the in vitro antibacterial and drug-potentiating effects of phytol against multidrug-resistant bacteria and to evaluate its in silico properties: ADME and molecular docking. Methods: The in vitro antibacterial activity of phytol and the phytol combined with conventional drugs was evaluated by microdilution tests against standard and resistant bacterial strains. Finally, the SwissADME platform was employed to analyse the physicochemical and pharmacokinetic characteristics of phytol. Results: Phytol significantly reduced the Minimum Inhibitory Concentration (MIC) of norfloxacin and gentamicin required to inhibit multidrug-resistant strains of Escherichia coli and Staphylococcus aureus, respectively. Additionally, ADME analysis revealed that phytol exhibits low toxicity and favourable pharmacokinetic properties; in addition, it is revealed through molecular docking that phytol showed a relevant affinity with the proteins 6GJ1 and 5KDR, however, with values lower than the drugs gentamicin and ampicillin. Conclusions: Collectively, these findings suggest that phytol holds potential as an effective adjuvant in combating antimicrobial resistance. Full article

Common wheat (Triticum aestivum L.) is one of the most valuable cereal crops worldwide. This study examined leaf extracts of 30 accessions of T. aestivum and its subspecies using 48 h maceration with methanol by GC-MS and GCxGC-MS. The plants were grown from seeds of the wheat genetics collection of the Wheat Genetics Sector of the Institute of Cytology and Genetics, SB RAS. The analysis revealed 263 components of epicuticular waxes, including linear and branched alkanes, aliphatic alcohols, aldehydes, ketones, β-diketones, carboxylic acids and their derivatives, mono- and diterpenes, phytosterols, and tocopherols. Hierarchical cluster analysis and principal component analysis were used to identify and visualize the differences between the leaf extracts of different wheat cultivars. Three clusters were identified, with the leading components being (1) octacosan-1-ol, (2) esters of saturated and unsaturated alcohols, and (3) fatty acid alkylamides, which were found for the first time in plant extracts. The results highlight the importance of metabolic studies in understanding the adaptive mechanisms and increasing wheat resistance to stress factors. These are crucial for breeding new-generation cultivars with improved traits. Full article

Drug-induced liver injury (DILI) represents a significant clinical challenge characterized by hepatic dysfunction following exposure to diverse medications. Methotrexate (MTX) is a cornerstone in treating various cancers and autoimmune disorders. However, the clinical utility of MTX is overshadowed by its ability to induce hepatotoxicity. The current study aims to elucidate the hepatoprotective effect of the alcoholic extract of Egyptian Araucaria heterophylla resin (AHR) on MTX-induced liver injury in rats. AHR (100 and 200 mg/kg) significantly decreased hepatic markers (AST, ALT, and ALP), accompanied by an elevation in the antioxidant’s markers (SOD, HO-1, and NQO1). AHR extract also significantly inhibited the TGF-β/NF-κB signaling pathway as well as the downstream cascade (IL-6, JAK, STAT-3, and cyclin D). The extract significantly reduced the expression of VEGF and p38 with an elevation in the BCL2 levels, in addition to a significant decrease in the IL-1β and TNF-α levels, with a prominent effect at a high dose (200 mg/kg). Using LC-HRMS/MS analysis, a total of 43 metabolites were tentatively identified, and diterpenes were the major class. This study presents AHR as a promising hepatoprotective agent through inhibition of the TGF-β/NF-κB and JAK/STAT3 pathways, besides its antioxidant and anti-inflammatory effects. Full article

The antitumor activity of different ent-kaurane diterpenes has been extensively studied. Several investigations have demonstrated the excellent antitumor activity of synthetic derivatives of the diterpene atractyligenin. In this research, a series of new synthetic amides and their 15,19-di-oxo analogues obtained from atractyligenin by modifying the C-2, C-15, and C-19 positions were designed in order to dispose of a set of derivatives with different substitutions at the amidic nitrogen. Using different concentrations of the obtained compounds (10–300 μM) a reduction in cell viability of HCT116 colon cancer cells was observed at 48 h of treatment. All the di-oxidized compounds were more effective than their alcoholic precursors. The di-oxidized compounds had already reduced the viability of two colon cancer cells (HCT116 and Caco-2) at 24 h when used at low doses (2.5–15 μM), while they turned out to be poorly effective in differentiated Caco-2 cells, a model of polarized enterocytes. The data reported here provide evidence that di-oxidized compounds induced apoptotic cell death, as demonstrated by the appearance of condensed and fragmented DNA in treated cells, as well as the activation of caspase-3 and fragmentation of its target PARP-1. Full article

A series of novel diterpene-type 1,3-aminoalcohols and their regioisomers have been synthesised from natural stevioside in a stereoselective manner. The key intermediate β-keto alcohol was prepared using Wagner–Meerwein rearrangement of the epoxide derived from steviol methyl ester. The primary aminoalcohol was formed via Raney-nickel-catalysed hydrogenation of an oxime, and a versatile library of aminoalcohols was synthesised using a Schiff base with the primary amines. The aminoalcohol regioisomers were prepared from the mesylate of the β-keto alcohols. The corresponding primary aminoalcohol was formed via the palladium-catalysed hydrogenation of hydroxyl-azide, and click reactions of the latter were also carried out. The new compounds were characterised using 1D- and 2D-NMR techniques and HRMS measurements. The in vitro investigations showed high inhibition of cell growth in human cancer cell lines (HeLa, SiHa, A2780, MCF-7 and MDA-MB-231) in the case of naphthalic N-substituted derivatives. The antiproliferative effects were assayed using the MTT method. Full article

Cladostephus spongiosus was harvested once a month during its growing season (from May to August) from the Adriatic Sea. Algal volatile organic compounds (VOCs) were obtained by headspace solid-phase microextraction (HS-SPME) and hydrodistillation (HD) and analysed by gas chromatography and mass spectrometry (GC-MS). The effects of air drying and growing season on VOCs were determined. Two different extraction methods (ultrasound-assisted extraction (UAE) and microwave-assisted extraction (MAE)) were used to obtain ethanolic extracts of C. spongiosus. In addition, the seasonal antioxidant potential of the extracts was determined, and non-volatile compounds were identified from the most potent antioxidant extract. Aliphatic compounds (e.g., pentadecane) were predominantly found by HS-SPME/GC-MS. Hydrocarbons were more than twice as abundant in the dry samples (except in May). Aliphatic alcohols (e.g., hexan-1-ol, octan-1-ol, and oct-1-en-3-ol) were present in high percentages and were more abundant in the fresh samples. Hexanal, heptanal, nonanal, and tridecanal were also found. Aliphatic ketones (octan-3-one, 6-methylhept-5-en-2-one, and (E,Z)-octa-3,5-dien-2-one) were more abundant in the fresh samples. Benzene derivatives (e.g., benzyl alcohol and benzaldehyde) were dominant in the fresh samples from May and August. (E)-Verbenol and p-cymen-8-ol were the most abundant in dry samples in May. HD revealed aliphatic compounds (e.g., heptadecane, pentadecanal, (E)-heptadec-8-ene, (Z)-heptadec-3-ene), sesquiterpenes (germacrene D, epi-bicyclosesquiphellandrene, gleenol), diterpenes (phytol, pachydictyol A, (E)-geranyl geraniol, cembra-4,7,11,15-tetraen-3-ol), and others. Among them, terpenes were the most abundant (except for July). Seasonal variations in the antioxidant activity of the ethanolic extracts were evaluated via different assays. MAE extracts showed higher peroxyl radical inhibition activity from 55.1 to 74.2 µM TE (Trolox equivalents). The highest reducing activity (293.8 µM TE) was observed for the May sample. Therefore, the May MAE extract was analysed via high-performance liquid chromatography with high-resolution mass spectrometry and electrospray ionisation (UHPLC-ESI-HRMS). In total, 17 fatty acid derivatives, 9 pigments and derivatives, and 2 steroid derivatives were found. The highest content of pheophorbide a and fucoxanthin, as well as the presence of other pigment derivatives, could be related to the observed antioxidant activity. Full article

Determination of chemotypes and of their role in the polymorphism of populations is an important field in the research on secondary metabolites of plants. In the present study, by gas chromatography coupled with mass spectrometry, the composition of bark extracts from rowan S. aucuparia subsp. sibirica was determined for 16 trees growing within Akademgorodok of Novosibirsk, with bark samples collected both in winter and summer. Among 101 fully or partially identified metabolites, there are alkanes, alkenes, linear alcohols, fatty acids and their derivatives, phenols and their derivatives, prunasin and its parent and derivative compounds, polyprenes and their derivatives, cyclic diterpenes, and phytosterols. These compounds were grouped according to their biosynthesis pathways. Cluster analysis revealed two groups among the bark samples collected in winter and three groups among bark samples collected in summer. The key determinants of this clustering are the biosynthesis of metabolites via the cyanogenic pathway (especially potentially toxic prunasin) and their formation via the phytosterol pathway (especially potentially pharmacologically useful lupeol). It follows from the results that the presence of chemotypes having sharply different profiles of metabolites in a population from a small geographic area invalidates the practice of general sampling to obtain averaged data when a population is described. From the standpoint of possible industrial use or plant selection based on metabolomic data, it is possible to select specific sets of samples containing a minimal amount of potentially toxic compounds and the largest amount of potentially useful substances. Full article

Plagiomnium acutum T. Kop. (P. acutum) has been used as a traditional Chinese medicine for thousands of years to treat cancer but lacks evidence. The objective of this work was to reveal the chemical composition of P. acutum essential oil (PEO) and explore its potential antitumor activity and molecular mechanism. PEO was prepared by the simultaneous distillation–extraction method and characterized by gas chromatography/mass spectroscopy. CCK8 assay, flow cytometry, western blot, and immunofluorescence techniques were used to analyze the effects and mechanism of PEO against cancer cells. A total of 74 constituents of PEO were identified, with diterpenes (26.5%), sesquiterpenes (23.89%), and alcohols (21.81%) being the major constituents. Two terpenoids, selina-6-en-4-ol and dolabella-3,7-dien-18-ol, were detected in PEO for the first time. PEO showed significant cell growth inhibitory activity on HepG2 and A549 cells by blocking the G1 phase and inducing apoptosis, which may be attributed to its upregulation of p21^Cip1 and p27^Kip1 proteins and interference with mitochondrial membrane potential effect. Dolabella-3,7-dien-18-ol accounts for 25.5% of PEO and is one of the main active components of PEO, with IC₅₀ values in HepG2 and A549 cells of (25.820 ± 0.216) µg/mL and (23.597 ± 1.207) μg/mL, respectively. These results confirmed the antitumor medicinal value of P. acutum and showed great application potential in the pharmaceutical industry. Full article

Abietic acid (AA), dehydroabietic acid (DHA) and triptoquinones (TQs) are bioactive abietane-type diterpenoids, which are present in many edible vegetables and medicinal herbs with health-promoting properties. Evidence suggests that beneficial effects of diterpenes operate, at least in part, through effects on cells in the immune system. Dendritic cells (DCs) are a key type of leukocyte involved in the initiation and regulation of the immune/inflammatory response and natural or synthetic compounds that modulate DC functions could be potential anti-inflammatory/immunomodulatory agents. Herein, we report the screening of 23 known semisynthetic AA and DHA derivatives, and TQs, synthesized previously by us, in a multi-analyte DC-based assay that detects inhibition of pro-inflammatory cytokine production. Based on the magnitude of the inhibitory effect observed and the number of cytokines inhibited, a variety of activities among compounds were observed, ranging from inactive/weak to very potent inhibitors. Structurally, either alcohol or methyl ester substituents on ring A along with the introduction of aromaticity and oxidation in ring C in the abietane skeleton were found in compounds with higher inhibitory properties. Two DHA derivatives and two TQs exhibited a significant inhibition in all pro-inflammatory cytokines tested and were further investigated. The results confirmed their ability to inhibit, dose dependently, LPS-stimulated expression of the co-stimulatory molecules CD40 and/or CD86 and the production of the pro-inflammatory cytokines IL-1β, IL-6, IL-12 and TNFα. Our results demonstrate that DC maturation process can be targeted by semisynthetic DHA derivatives and TQ epimers and indicate the potential of these compounds as optimizable anti-inflammatory/immunomodulatory agents. Full article

The present study aimed to isolate volatile organic compounds (VOCs) from fresh (FrHSc) and air-dried (DrHSc) Halopteris scoparia (from the Adriatic Sea) by headspace solid-phase microextraction (HS-SPME) and hydrodistillation (HD) and to analyse them by gas chromatography and mass spectrometry (GC–MS). The impact of the season of growth (May–September) and air-drying on VOC composition was studied for the first time, and the obtained data were elaborated by principal component analysis (PCA). The most abundant headspace compounds were benzaldehyde, pentadecane (a chemical marker of brown macroalgae), and pentadec-1-ene. Benzaldehyde abundance decreased after air-drying while an increment of benzyl alcohol after drying was noticed. The percentage of pentadecane and heptadecane increased after drying, while pentadec-1-ene abundance decreased. Octan-1-ol decreased from May to September. In HD-FrHSc, terpenes were the most abundant in June, July, and August, while, in May and September, unsaturated aliphatic compounds were dominant. In HD-DrHSc terpenes, unsaturated and saturated aliphatic compounds dominated. (E)-Phytol was the most abundant compound in HD-FrHSc through all months except September. Its abundance increased from May to August. Two more diterpene alcohols (isopachydictyol A and cembra-4,7,11,15-tetraen-3-ol) and sesquiterpene alcohol gleenol were also detected in high abundance. Among aliphatic compounds, the dominant was pentadec-1-ene with its peak in September, while pentadecane was present with lower abundance. PCA (based on the dominant compound analyses) showed distinct separation of the fresh and dried samples. No correlation was found between compound abundance and temperature change. The results indicate great seasonal variability of isolated VOCs, as well among fresh and dried samples, which is important for further chemical biodiversity studies. Full article

The present research is a comprehensive investigation of Dasycladus vermicularis (Scopoli) Krasser 1898 from the Adriatic Sea (Croatia) regarding volatilome–volatile organic compounds (VOCs, mostly nonpolar compounds) and less polar nonvolatile compounds for the first time. Headspace solid-phase microextraction (HS-SPME) and hydrodistillation (HD) were used showing the great volatilome variability among fresh (HS-FrDV and HD-FrDV) and dried (HS-DrDV and HD-DrDV) samples after GC–MS analysis. Aromatic aldehydes were dominant in both fresh and air-dried HS samples with benzaldehyde as the most abundant in fresh samples and decreasing 2.7–3.7 times after drying together with 2-phenylbut-2-enal that was not present after drying. Aliphatic compounds (unsaturated hydrocarbons in HS-FrDV; saturated hydrocarbons in HS-DrDV) were also present. C₁₁-hydrocarbons (dictyopterpene C’ and dictyopterpene D’) were detected in HS-FrDV. (E)-Phytol was the most dominant compound in HD-FrDV and HD-DrDV. Diterpene alcohols (cembra-4,7,11,15-tetraen-3-ol and (Z)-falcarinol) and sesquiterpene alcohol, cubenol, were dominant in HD-FrDV, and their abundance decreased after drying. C₁₃-norisoprenoides (α-ionone and β-ionone) increased after drying. Aliphatic compounds were present in both HD-FrDV and HD-DrDV samples. The less polar nonvolatile compounds in the obtained fractions F3 and F4 were analysed and identified by UHPLC-ESI(+)-HRMS. Identified compounds belonged to a group of pigments (7 compounds), fatty acid derivatives (13 compounds), as well as steroids and terpenes (10 compounds). Porphyrin-based compounds (C₅₅H₇₄N₄O_5–7), xanthophylls, sphingolipid compounds, fatty acid amides, and phytosterols represented the majority of identified compounds. By implementing both in vitro and in vivo assays for antioxidant activity determination, F3 showed a higher activity than F4. Inhibitory concentrations (IC₅₀) for F3 and F4 were 498.00 ± 0.01 µg/mL and 798.00 ± 0.81 µg/mL, respectively, while a 1.5-fold reduction in the ROS level was observed after pre-treatment of zebrafish larvae with 45 µg/mL of F3. Full article

Spodoptera frugiperda J.E. Smith (Lepidoptera: Noctuidae) is a polyphagous insect pest native to America. Due to its capacity for adaptation and migration, it is currently located in Africa, Asia, and Oceania, where it threatens agricultural crops. The ability of S. frugiperda to develop resistance to insecticides is one of the reasons for the continuous search for more effective, low-cost, and environmentally friendly control products. In the present work, the insecticidal activity of ethanolic and hexane extracts obtained from fresh and dehydrated leaves of Piper auritum Kunth (Piperales: Piperaceae), Piper umbellatum L. (Piperales: Piperaceae), and Cedrela odorata L. (Sapindales: Meliaceae) was studied against first instar larvae of S. frugiperda. The ethanolic extracts of the dehydrated leaves of C. odorata and P. auritum presented insecticidal activity as high (100% mortality at a concentration of 92 mg/cm²) as that obtained with the positive control, Melia azedarach L. (Sapindales: Meliaceae). The GC-MS analysis of the extracts revealed the presence of phytochemicals classified mainly into the groups of monoterpenes, sesquiterpenes, diterpenes, phenylpropanoids, alcohols, and fatty acids. P. auritum grows and propagates rapidly. In addition, due to its low toxicity in mammals and non-target insects, it is a plant with the potential to be used as a botanical insecticide. The exposure of S. frugiperda larvae to low concentrations of ethanolic extract of P. auritum allowed us to observe their biological activity in the development of this insect. The LC₅₀ was 22.1 mg/cm². At sublethal concentrations (LC₂₁ and LC₃₅) the low fertility of the emerging adults was noticeable. Full article

Forest fires are one of the main environmental threats in Chile. Fires in this Mediterranean climate region frequently affect native forests and exotic plantations, including in several cases urban and rural settlements. Considering the scarcity of information regarding the fire response dynamics of tree species that are frequently affected by fires, this study aims to establish a flammability classification according to the evolution of the fire initiation risk presented by the most affected forest species in the Valparaíso region. Three exotic species, Eucalyptus globulus, Pinus radiata, and Acacia dealbata, and two native species, Cryptocarya alba and Quillaja saponaria, were studied. Flammability assays indicate that E. globulus, A. dealbata, and C. alba are extremely flammable, whereas P. radiata and Q. saponaria are flammable. Furthermore, E. globulus and A. dealbata have the highest heating values while Q. saponaria has the lowest values. The extreme flammability of E. globulus, A. dealbata, and C. alba indicates a high susceptibility to ignite. Furthermore, the high heat of combustion of E. globulus and A. dealbata can be associated with a high energy release, increasing the risk of fires spreading. In contrast, Q. saponaria has the lowest predisposition to ignite and capacity to release heat. Accordingly, this work shows that all studied tree species contain organic metabolites that are potentially flammable (sesquiterpenes, aliphatic hydrocarbons, alcohol esters, ketones, diterpenes, and triterpenes) and can be considered as drivers of flammability in vegetation. Finally, these preliminary results will aid in the construction of more resilient landscapes in the near future. Full article

When exposed to stressful conditions, plants produce numerous volatile organic compounds (VOCs) that have different biological and environmental functions. VOCs emitted during the rehydration process by the fronds of desiccation tolerant fern Asplenium ceterach L. were investigated. Headspace GC–MS analysis revealed that the volatiles profile of rustyback fern is mainly composed of fatty acid derivatives: isomeric heptadienals (over 25%) and decadienals (over 20%), other linear aldehydes, alcohols, and related compounds. Aerial parts of the rustyback fern do not contain monoterpene-type, sesquiterpene-type, and diterpene-type hydrocarbons or corresponding terpenoids. Online detection of VOCs using proton-transfer reaction mass spectrometry (PTR–MS) showed a significant increase in emission intensity of dominant volatiles during the first hours of the rehydration process. Twelve hours after re-watering, emission of detected volatiles had returned to the basal levels that corresponded to hydrated plants. During the early phase of rehydration malondialdehyde (MDA) content in fronds, as an indicator of membrane damage, decreased rapidly which implies that lipoxygenase activity is not stimulated during the recovery process of rustyback fern. Full article