Terpenoid Compounds Research Articles

Bioactivity and Metabolomic Profile of Extracts Derived from Mycelial Solid Cultures of Hypsizygus marmoreus.

The beech mushroom (Hypsizygus marmoreus) is a highly nutritious, edible medicinal mushroom native to East Asia. The present research investigated the impact of different substrates on the metabolite compositions of H. marmoreus mycelia cultivated in vitro. The substrates tested included malt extract agar, malt extract agar enriched with barley malt, and malt extract agar enriched with grape pomace. The study also assessed antimicrobial and antiradical activities of the extracts against gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus), gram-negative bacteria (Escherichia coli, Salmonella typhi, and Pseudomonas aeruginosa), yeasts (Candida albicans, C. tropicalis, and C. parapsilosis), and dermatophytes (Trichophyton mentagrophytes, T. tonsurans, T. rubrum, Arthroderma quadrifidum, A. gypseum, A. curreyi, and A. insingulare). The results revealed that the H. marmoreus mycelia extracts demonstrated antibacterial and antifungal activities against the tested microorganisms. Extracts obtained from the cultivation in substrates enriched with either barley malt or grape pomace exhibited the highest antibacterial activity among all the tested bacterial strains except for P. aeruginosa. The same extracts showed the highest inhibitory effect against C. albicans and C. parapsilosis. Noteworthy, the extract from the mushroom cultivated in the substrate enriched with grape pomace also exhibited remarkable efficacy against T. mentagrophytes and T. tonsurans. Terpenoid and carbapenem compounds could be related to the antimicrobial properties of the extracts from mushrooms cultivated in substrates enriched with grape pomace. In comparison, the higher antiradical properties could be related to the content of indole compounds. In conclusion, growth substrate selection affects the nutritional and medicinal properties of H. marmoreus, making it a valuable contribution to the understanding of the cultivation of this mushroom.

De novo transcriptome profiling and development of novel secondary metabolites based genic SSRs in medicinal plant Phyllanthus emblica L. (Aonla)

Phyllanthus emblica (Aonla, Indian Gooseberry) is known to have various medicinal properties, but studies to understand its genetic structure are limited. Among the various secondary metabolites, ascorbic acid, flavonoids, terpenoids, phenols and tannins possess great potential for its pharmacological applications. Keeping this consideration, we assembled the transcriptome using the Illumina RNASeq500 platform, generating 39,933,248 high-quality paired-end reads assembled into 1,26,606 transcripts. A total of 87,771 unigenes were recovered after isoforms and unambiguous sequences deletion. Functional annotation of 43,377 coding sequences against the NCBI non-redundant (Nr) database search using BlastX yielded 38,692 sequences containing blast hits and found 4685 coding sequences to be unique. The transcript showed maximum similarity to Hevea brasilensis (16%), followed by to Jatropha curcas (12%). Considering key genes involved in the biosynthesis of flavonoids and various classes of terpenoid compounds, thirty EST-SSR primer sequences were designed based on transcriptomic data. Of which, 12 were found to be highly polymorphic with an average of 86.38%. The average value for marker index (MI), effective multiplicity ratio (EMR), resolution power (Rp) and polymorphic information content (PIC) was 7.20, 8.34, 8.64 and 0.80, respectively. Thus, from this study, we developed newly EST-SSRs linked to important genes involved in the secondary metabolites biosynthesis that will be serving as an invaluable genetic resource for crop improvement including the selection of elite genotypes in P. emblica and its closely related Phyllanthaceae species.

Unraveling the evolutionary dynamics of the TPS gene family in land plants.

Terpenes and terpenoids are key natural compounds for plant defense, development, and composition of plant oil. The synthesis and accumulation of a myriad of volatile terpenoid compounds in these plants may dramatically alter the quality and flavor of the oils, which provide great commercial utilization value for oil-producing plants. Terpene synthases (TPSs) are important enzymes responsible for terpenic diversity. Investigating the differentiation of the TPS gene family could provide valuable theoretical support for the genetic improvement of oil-producing plants. While the origin and function of TPS genes have been extensively studied, the exact origin of the initial gene fusion event - it occurred in plants or microbes - remains uncertain. Furthermore, a comprehensive exploration of the TPS gene differentiation is still pending. Here, phylogenetic analysis revealed that the fusion of the TPS gene likely occurred in the ancestor of land plants, following the acquisition of individual C- and N- terminal domains. Potential mutual transfer of TPS genes was observed among microbes and plants. Gene synteny analysis disclosed a differential divergence pattern between TPS-c and TPS-e/f subfamilies involved in primary metabolism and those (TPS-a/b/d/g/h subfamilies) crucial for secondary metabolites. Biosynthetic gene clusters (BGCs) analysis suggested a correlation between lineage divergence and potential natural selection in structuring terpene diversities. This study provides fresh perspectives on the origin and evolution of the TPS gene family.

Soil uptake of isoprenoids in a Eucalyptus urophylla plantation forest in subtropical China

The exchange of isoprenoids, which includes isoprene, monoterpenes, and sesquiterpenes, between ecosystem soils and the atmosphere plays a significant role in soil ecology and atmospheric chemistry. However, research on flux exchange rates in subtropical ecosystems has been limited, as previous studies have mainly focused on temperate and boreal environments. In this study, we aimed to quantify the exchange of isoprenoids between the soil (with or without surface litter) and the atmosphere in a subtropical Eucalyptus urophylla plantation forest during the daytime in the wet season of subtropical China. Additionally, we investigated the influence of soil and litter variables on the fluxes of isoprenoids. Our results unveiled the exchange of isoprene and 17 terpenoid compounds, comprising 11 monoterpenes and 6 sesquiterpenes, between the studied soils and the atmosphere. Interestingly, regardless of the presence of surface litter, the studied soils acted as net sinks for isoprenoids, with isoprene being the most absorbed compound (−71.84 ± 8.26 μg m−2 h−1). The removal of surface litter had a significant impact on the exchange rates of two monoterpenes (α-pinene and β-pinene), resulting in decreased fluxes. Furthermore, the exchange rates of isoprene were positively correlated with litter dry weight and negatively correlated with soil temperature. The higher exchange rates of monoterpenes and sesquiterpenes were associated with increased levels of soil respiration and the abundance of leaf litter. These findings suggest that, in the context of projected global warming scenarios, the capacity of subtropical soils to act as sinks for isoprenoids is expected to increase in subtropical China. These changes in sink capacity may have implications for regional-scale atmospheric chemistry and ecosystem functioning.

Terpenoids from Euphorbiaceae as a source of antimalarial medicines: A literature review

Background: Malaria is an infectious disease caused by the Plasmodium parasite and transmitted by the Anopheles mosquito. Plasmodium falciparum is a parasite that causes the most deaths. Currently, there is resistance to various antimalarial drugs. For this reason, it is necessary to search for new antimalarial agents. Medicinal plants have been shown to play an important role in treating malaria for thousands of years. Some of Euphorbiaceae family plants contains terpenoid compounds, which are compounds with antimalarial activity. Objective: The present review aims to provide an overview of the terpenoid compounds from Euphorbiaceae family as an antimalarial. Method: Comprehensive information on Euphorbiaceae family from 2002-2022 was searched for literature relevant to major science-based data, including Scopus, Science, ScienceDirect, Pubmed, and SciFinder, using appropriate keyword combinations. Result: A total of 15 papers were included in this review. The terpenoids isolated from 14 species of Euphorbiaceae family and reported to possess antimalarial activity are presented. Conclusion: Terpenoids are found in almost all parts of Euphorbiaceae family plants and are reported to have moderate to high antimalarial activity. Screening of antimalarial terpenoid activity in Ephorbiaceae family plants can be a key step in the source and development of new antimalarial drugs.

Antibacterial activity of thymoquinone derivative

Natural products such as terpenoidal compounds have been extremely tested against pathogenic bacteria. Researches are frequently carried out to find out new natural, semisynthetic and synthetic antibacterial agents due to problems of resistance. Thymoquinone derivative was obtained in our previous study and the current research is a continuation. The antibacterial activity of a monoterpenoid; thymoquinone derivative, 5-isopropyl-2-methyloxepine-1-one (1) has been evaluated for the first time by following the Agar cup bioassay method employed. The bacterial strains used in this study were Escherichia coli and Bacillus subtilis. Compound 1 showed moderate activity against Gram-positive organism; B. subtilis and good activity against Gram-negative species; E. coli with zones of inhibition (ZOI) 10.0 ± 0.2 mm and 11.0 ± 0.2 mm against E. coli and B. subtilis, respectively, and in comparison with antibiotic, imipenem. The zones of inhibition were calculated as the mean of the triplicate. The antibacterial activity of thymoquinone derivative 1 could be explained by the presence of unsaturated lactone.

Isolation and Characterization of Secondary Metabolites in Ethyl Acetate Fraction From Indonesian Eucheuma Spinosum

AbstractEucheuma spinosum is a type of red algae (Eucheuma) which is used as a food which has a high source of carrageenan. Information on secondary metabolites in E. spinosum is known to have bioactive properties as an antioxidant and antibacterial. The purpose of this study was to isolate and characterize secondary metabolites in E.spinosum. The study was started by isolating secondary metabolites from E.spinosum using Soxhlet extraction followed by solvent partitioning, fractionation and characterization. The rendemen from methanol extract was 6.07% while the highest partition result was in the ethyl acetate fraction, which was 1.25%. Fractionation was carried out by column chromatography resulting in 2 single spots F401 and A402. Pure isolate F401 has an Rf value of 0.71 in the form of a white solid, A401 has an Rf value of 0.67 in the form of a brown gel. The results of characterization of isolates with a UV-Vis spectrophotometer obtained maximum absorption and absorbance values of F401 218.50 nm 4.79 M-1 cm-1, 273 nm 1.06 M-1 cm-1 respectively. Isolate A402 233.50 nm 4.1 M-1 cm-1, 407 nm 1.03 M-1 cm-1. Identification using FT-IR found that both isolates showed the presence of functional groups =C-H, C-C, C=O, C-H. According to the result of the UV and FT-IR spectra, two isolates can be identified as terpenoid compounds. Keywords: E.spinosum, Secondary Metabolites, Ethyl acetate fraction, UV-VIS, FT-IR

Terpenoid compounds from the fruits of Solanum virginianum.

Eleven compounds were isolated and identified from ethanolic extracts of Solanum virginianum fruits, including two new compounds (1-2) and nine known compounds (3-11). Their structures were determined tobemelongenaterpene C15-O-β-D-glucopyranoside (1), (9Z)-3,7,11,15-tetramethyl -hexadeca-1,6,10-triene-3,5,14,15-tetraol-5-O-β-D-glucopyranoside (2), actini-dioionoside A (3), byzantionoside B (4), citroside A (5), 7Z-roseoside (6), matenoside A (7), megastigmane (8), dihydrophaseic acid 3'-O-β-D-glucopyranoside (9), taraxerol (10), and huzhangoside C (11). In this paper, NMR spectroscopy was used to study the structures of the compounds, comparing their data with those in the literature. In addition, the potential anti-inflammatory activity of the compounds was also evaluated using the RAW264.7 cell inflammation model induced by lipopolysaccharide (LPS). The terpenoids showed no significant anti-inflammatory activity.

Phenolics and Terpenoids Profiling in Diverse Loquat Fruit Varieties and Systematic Assessment of Their Mitigation of Alcohol-Induced Oxidative Stress.

To compare and investigate the phenolic compounds in the peel and flesh of loquat (Eriobotrya japonica) and evaluate their ability to protect against alcohol-induced liver oxidative stress, we employed a combination of ultra-performance liquid chromatography (UPLC) and high-resolution mass spectrometry (HRMS) to qualitatively and quantitatively analyze 22 phenolics and 2 terpenoid compounds in loquat peel and flesh extracts (extraction with 95% ethanol). Among these, six compounds were identified for the first time in loquat, revealing distinct distribution patterns based on variety and tissue. Various chemical models, such as DPPH, FRAP, ORAC, and ABTS, were used to assess free radical scavenging and metal ion reduction capabilities. The results indicate that peel extracts exhibited higher antioxidant capacity compared with flesh extracts. Using a normal mouse liver cell line, AML-12, we explored the protective effects of loquat extracts and individual compounds against ethanol-induced oxidative stress. The findings demonstrate the enhanced cell viability and the induction of antioxidant enzyme activity through the modulation of Nrf2 and Keap1 gene expression. In a C57/BL6 mouse model of alcohol-induced liver damage, loquat extract was found to alleviate liver injury induced by alcohol. The restoration of perturbed serum liver health indicators underscored the efficacy of loquat extract in reclaiming equilibrium. The culmination of these findings significantly bolsters the foundational knowledge necessary to explore the utilization of loquat fruit extract in the creation of health-focused products.

Isolasi Dan Identifikasi Terpenoid Fraksi Heksan Daun Premna serratifolia L. Menggunakan GC-MS

Buas-buas (Premna serratifolia L.) is a plant that belongs to the Verbenaceae family. Terpenoid compounds that exist in buas-buas plants have bioactivity as medicine. Terpenoid compounds are soluble compounds in n-hexane. The purpose of this study was to isolate and identify the terpenoid compounds contained in the n-hexane fraction of buas-buas leaves using the GC-MS method. The buas-buas leaves were macerated with 96% ethanol solvent and then fractionated using a separating funnel with n-hexane as solvent. The n-hexane fraction of buas-buas leaves was isolated using column chromatography with a gradient mobile phase combination of n-hexane and ethyl acetate, then identified using the GC-MS instrument. The terpenoid compounds found in the n-hexane fraction of buas-buas leaves are estimated to be neophytadiene; 3,7,11,15-tetramethyl-2-hexadecen-1-ol; and 2 hydroxy-4a,5-dimethyl-3-(prop-1-en-2-yl) octahydronaphthalen-1-(2H)-one.

The Antibacterial Potential of Essential Oils of Oral Care Thai Herbs against Streptococcus mutans and Solobacterium moorei—In Vitro Approach

Oral malodor, often known as halitosis, is an irritating breath odor that originates in the mouth and can cause significant psychological and social distress. Chlorhexidine, a powerful antimicrobial agent effective against bacteria and fungi, has become the standard treatment for halitosis. However, it has drawbacks including altered taste perception, dry mouth, and more noticeable dental staining. The use of natural essential oils to avoid these unwanted effects has proven to be an attractive strategy. This study aims to evaluate the potential of four essential oils consisting of Ma-kwean fruit (Zanthoxylum limonella, MK), clove bud (Syzygium aromaticum, CV), star anise fruit (Illicium verum, SA) and cinnamon bark (Cinnamomum aromaticum, CM) for the purpose of combating bad breath by assessing their antibacterial efficacy against halitosis-associated bacteria (Streptococcus mutans and Solobacterium moorei). The hydro-distillation process was used to prepare the essential oils, which were obtained as yellowish to colorless liquids with yields of 6.58 ± 0.81, 12.21 ± 2.98, 4.29 ± 0.15 and 1.26 ± 0.09% for MK, CV, SA and CM, respectively. The terpenoid compounds terpinene-4-ol (47.04%), limonene (17.19%), sabinene (13.27%) and alpha-terpineol (6.05%) were found as the main components in MK essential oil, while phenylpropanoids were identified as the primary components of other essential oils, namely trans-cinnamaldehyde (83.60%), eugenol (83.59%) and anethol (90.58%) were identified as the primary components of CM, CV and SA essential oils, respectively. For the antibacterial properties, the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) values were investigated. CM essential oil exhibited the greatest capacity to inhibit growth and eradicate S. mutans, with MIC and MBC values of 0.039%, followed by CV (MIC of 0.078% and MBC of 0.156%) and MK (MIC and MBC of 0.156%), whereas the MIC of SA was 1.250% without eradication. Both CM and CV essential oils demonstrated exceptional efficacy against S. moorei, with MIC and MBC values of 0.019% and 0.033%, respectively. Furthermore, the inhibition of S. moorei biofilm formation was investigated and we discovered that the lowest effective concentration necessary to eliminate the S. moorei biofilm was one quarter of the MIC for MK, CM and CV, while that for SA essential oil was half of the MIC. These encouraging results suggest that the incorporation of MK, CM and CV essential oils into oral care products could potentially enhance their efficacy in halitosis treatment.

AKTIVITAS ANTIRAYAP DARI EKSTRAK METANOL GUBAL KAYU GAHARU BUAYA (Aetoxylon sympetalum) TERHADAP RAYAP TANAH (Coptotermes sp.) (ANTITERMITE ACTIVITY OF METHANOL EXTRACT AGARWOOD BUAYA (Aetoxylon sympetalum) ON SUBTERRANEAN TERMITES (Coptotermes sp.))

Agarwood buaya (Aetoxylon sympetalum) is a Kalimantan endemic plant whose utilization has not been optimal. This plant has potential as an anti-termite, one of which is sapwood. This study aims to determine the content of secondary metabolites from the results of phytochemical screening, components of agarwood buaya sapwood based on GC-MS analysis fraction n-hexane and anti-termite activity against subterranean termites (Coptotermes sp.). Research that has been done is divided into four steps, maceration and fractionation, phytochemical screening, GC-MS analysis, and testing the activity of termites using a forced feeding test method. Crude methanol extract from 1 kg of dried agarwood buaya sapwood was 240.787 g (24.0787%), consisting of 0.8339% n-hexane fraction, 86.3663% chloroform fraction, and 0.7571% methanol fraction. The results of phytochemical screening on agarwood buaya sapwood extract showed that it contained flavonoid, terpenoid, steroid, and phenolic compounds. Identification of the components of agarwood buaya sapwood fraction n-hexane through GC-MS yielded compounds a4-chloro-6-methoxy-2-methylquinolin-8-amine (10.33%), stigmasterol among other (5.94%), n-hexa-decanoic acid (3.2%), 6-octa-decenoic acid (2.99%), and 1,2-Benzene-diol, 3,5-bis(1,1-dimethyl-ethyl) (2.01%). Termite activity test was carried out for 3 days with variations in the concentration of 0% (negative control), 0.1%, 0.2%, 0.3%, 0.4% (w/v), and 0.25% (v/v) (fibronil as positive control). The results of anti-termite testing show the most active fraction was the methanol fraction (LC50 0.146%) followed by the chloroform fraction (LC50 0.167%), methanol crude extract (LC50 0.192%), and the n-hexane fraction (LC50 0.208%).

Malacitanolide, reissantin E and paclitaxel compounds as inhibitors of envelope, NS5 and NS2B/NS3 target proteins of dengue virus: Computational docking and molecular dynamics simulations studies

ObjectiveThe objective of this study is to find out the role of terpenoid compounds as potential inhibitors against certain protein targets of dengue virus. MethodsThe 2-dimensional structures of terpenoid compounds were retrieved from the PubChem database. They were analysed for their interactions with target proteins of dengue virus such as envelope (1OKE), NS5 (1R6A-RPV & SHA) and NS2B/NS3 (4M9K) by docking studies followed by molecular dynamics (MD) simulations using Schrödinger software, version 10.7. ResultsOut of 513 terpenoid compounds studied, malacitanolide showed the highest interaction energy values of −7.072 kcal/mol (hydrogen bond (HB) interactions with Thr280, Gln200, Gln271, Gln49 and Ala50), −5.295 kcal/mol (HB interactions with Ser150, Lys29, Ser214) and −4.030 kcal/mol (HB interactions with Glu1169 and Asn1119) against 1OKE, 1R6A-RPV and 4M9K targets, respectively. Paclitaxel had shown the interaction energy value of −9.334 kcal/mol (HB with Lys61, Asp146, Trp87, Gly148, and Arg84) with 1R6A-SAH. MD simulation studies revealed that the best interacting compound malacitanolide maintained a stable complex with 1OKE of dengue virus. Malacitanolide, reissantin E, and paclitaxel exhibited very good interactions with all three-protein targets of dengue virus and had also shown significant stability. ConclusionsIn the present study, it is concluded that the terpenoid compounds malacitanolide, reissantin E, and paclitaxel could act as potential inhibitors against all three target proteins of dengue virus.

The Nighttime Fragrance of Guettarda scabra (Rubiaceae): Flower Scent and Its Implications for Moth Pollination.

Floral scent is crucial for attracting pollinators, especially in plants that bloom at night. However, chemical profiles of flowers from nocturnal plants with varied floral morphs are poorly documented, limiting our understanding of their pollination ecology. We investigated the floral scent in Guettarda scabra (L.) Vent. (Rubiaceae), a night-blooming species with short- and long-styled floral morphs, found in the threatened pine rocklands in south Florida, US. By using dynamic headspace sampling and GC-MS analysis, we characterized the chemical profiles of the floral scent in both morphs. Neutral red staining was also employed to determine the specific floral regions responsible for scent emission in G. scabra. The results revealed that G. scabra's fragrance consists entirely of benzenoid and terpenoid compounds, with benzeneacetaldehyde and (E)-β-ocimene as dominant components. There were no differences in the chemical profiles between the long- and short-styled flowers. Staining assays indicated that the corolla lobes, anthers, and stigma were the primary sources of the scent. These findings indicate that G. scabra's floral scent is consistent with that of night-blooming plants pollinated by nocturnal hawkmoths, providing important insights into its chemical ecology and pollinator attraction. This study demonstrates how floral scent chemistry can validate predictions based on flower morphology in hawkmoth-pollinated plants.

Research Article: Isolasi dan Identifikasi Senyawa Terpenoid

Terpenoids are a group of hydrocarbons that are produced in large quantities by plants and are mainly contained in the sap and cell vacuoles. In plants, terpene compounds and their modifications, terpenoids, are secondary metabolites. Terpenoids make up many of the essential oils produced by plants. The content of essential oils influences the use of spice products, both as seasonings, as fragrances, as well as ingredients for medicine, health, etc. The terpenoid-steroid test was carried out using the Lieberman-Buchard reagent which yielded positive results for terpenoids for all fractions. The results obtained for the n-hexane and ethyl acetate fractions on the addition of lieberman-buchard yielded positive results for steroids as indicated by the formation of a green color in the fractions. The purpose of this research article is to provide information to find out what methods are used in isolation in identifying terpenoid compounds and knowing the types of terpenoid compounds obtained from the results of previous research journals.

The effect of a small polyphenolic and terpenoids phytochemical constituent on curing and preventing of Covid-19 infections

Covid-19 spreading have caused millions of deaths worldwide and caused sever economic shrinking resulted in high levels of inflations. The on going pandemic has pushed the pharmaceutical companies to invent different vaccines to overcome the spreading of the virus and to reduce its effect on health and economy. Unfortunately, the middle and low income countries have been struggling in providing vaccines to their people due to the high expenses associated with vaccines ordering. Thus, the interest in finding a treatment and a prevention of Covid-19 from natural products has increased not in those countries only, even in high income countries. In this review we investigated the promising natural phytochemical compounds and their published mechanism of action in a prestigious peer-reviewed research journal throw different molecular docking and in vivo and vitro techniques. Its was found that the consumption of the medicinal plants containing small phenolic and terpenoids phytoconstituent like as thymoquinone, quercetin, caffeic acid, ursolic acid, ellagic acid, vanillin, and thymol have a great therapeutic effect for curing and preventing viral infections. This review has focused on the small polyphenolic and terpenoids compounds and their potential and mechanism activity against SARS-CoV-2. Our comprehensive analysis provides mechanistic insight into plant components for virus containment prevent infections and provide better solutions through natural therapeutically active ingredients.

Antimicrobial Potential of Aqueous Extract of Giant Sword Fern and Ultra-High-Performance Liquid Chromatography-High-Resolution Mass Spectrometry Analysis.

Vibriosis and parasitic leech infestations cause the death of various farmed fish, such as groupers, hybrid groupers, sea bass, etc., in Malaysia and other Southeast Asian countries. In the absence of natural control agents, aquaculture operators rely on toxic chemicals to control Vibrio infections and parasitic leeches, which can have a negative impact on the environment and health. In the present study, we investigated the antivibrio and antiparasitic activities of the aqueous extract of giant sword fern (GSF) (Nephrolepis biserrata, Nephrolepidaceae, locally known as "Paku Pedang") against four Vibrio spp. and the parasitic leech Zeylanicobdella arugamensis, as well as its metabolic composition using the ultra-high-performance liquid chromatography-high-resolution mass spectrometry system (UHPLC-HRMS). The data show that the aqueous extract of GSF at a concentration of 100 mg/mL exhibits potent bactericidal activity against V. parahaemolyticus with a zone of inhibition of 19.5 mm. In addition, the extract showed dose-dependent activity against leeches, resulting in the complete killing of the parasitic leeches within a short period of 11-43 min when tested at concentrations ranging from 100 to 25 mg/mL. The UHPLC-HRMS analysis detected 118 metabolites in the aqueous extract of GSF. Flavonoids were the primary metabolites, followed by phenolic, aromatic, fatty acyl, terpenoid, vitamin and steroidal compounds. Notably, several of these metabolites possess antibacterial and antiparasitic properties, including cinnamaldehyde, cinnamic acid, apigenin, quercetin, cynaroside, luteolin, naringenin, wogonin, 6-gingerol, nicotinamide, abscisic acid, daidzein, salvianolic acid B, etc. Overall, our study shows the significant antibacterial and antiparasitic potential of the GSF aqueous extract, which demonstrates the presence of valuable secondary metabolites. Consequently, the aqueous extract is a promising natural alternative for the effective control of Vibrio infections and the treatment of parasitic leeches in aquaculture systems.

Covalent Conjugates of Allylbenzenes and Terpenoids as Antibiotics Enhancers with the Function of Prolonged Action.

The drug resistance of pathogenic bacteria is often due efflux pumps-specific proteins that remove foreign compounds from bacterial cells. To overcome drug resistance, adjuvants are often used that can inhibit efflux pumps or other systems that ensure the resistance of bacteria to the action of antibiotics. We assumed that a new level of effectiveness with the use of an antibiotic + an adjuvant pair could be achieved by their joint delivery into the pathogen. To test this hypothesis, we constructed a series of molecular carriers based on poly-(olygo-, dendry)mers based on cyclodextrin-grafted PEI or mannan, as well as glycol chitosan, covalently bound to antibiotic, adjuvant, and the oligosaccharide ligand to the macrophage mannose receptor (CD206), which we studied earlier and showed high efficiency and selectivity of delivery of a therapeutic "cargo" to macrophages. Moxifloxacin was used as an antibiotic, and terpenoid and allylbenzene compounds were used as adjuvants, for which we previously discovered the ability to inhibit bacterial efflux pumps. We show that: (a) the resulting structures were stable in vitro for a long time (up to 10 days); (b) they were adsorbed on bacterial cells, providing a local increase in the concentration of the antibiotic and adjuvant in pathogen cells; (c) they were internalized by bacterial cells, ensuring the accumulation of both antibiotic and adjuvant inside bacterial cells; (d) the adjuvant, after entering the bacterial cell, provided inhibition of the efflux pumps; (e) due to this action of the adjuvant, combined with the targeted delivery by the carrier, the antibiotic's half-life in rats increased by more than 2 times, the effective concentration of the drug in the blood plasma (AUC) increased up to 8-10 times; (f) a significant increase in the effectiveness of the antibacterial action against Gram+ and Gram- cells was achieved (up to 3 times). Potentially, such an approach would significantly increase the effectiveness of therapies for a number of infectious and other diseases, reduce the dosage of antibiotics, shorten the duration of treatment, and reduce the risk of developing bacterial resistance. Moreover, the use of a polymer carrier with covalently bound organic molecules of different structures will avoid problems linked to different (suboptimal) solubility and bio-distribution of the administered molecules, which would be almost inevitable when using the same compounds separately. It would be very difficult to find antibiotic/adjuvant pairs that simultaneously achieve optimal concentrations in the same target cells. In our case, terpenoids and alkylbenzenes used as adjuvants are practically insoluble as individual compounds, and their unacceptable pharmacological properties would not allow them to be used as efflux pump inhibitors.

Identification of terpenoids as potential inhibitors of SARS-CoV-2 (main protease) and spike (RBD) via computer-aided drug design

The scientific community has been faced with a major challenge in the fight against the SARS-CoV-2 virus responsible for the COVID-19 pandemic, due to the lack of targeted antiviral drugs. To address this issue, we used an in silico approach to screen 23 natural compounds from the terpenoid class for their ability to target key SARS-CoV-2 therapeutic proteins. The results revealed that several compounds showed promising interactions with SARS-CoV-2 proteins, specifically the main protease and the spike receptor binding domain. The molecular docking analysis revealed the importance of certain residues, such as GLY143, SER144, CYS145 and GLU166, in the main protease of the SARS-CoV-2 protein, which play a crucial role in interactions with the ligand. In addition, our study highlighted the importance of interactions with residues GLY496, ARG403, SER494 and ARG393 of the spike receptor-binding domain within the SARS-CoV-2 protein. ADMET and drug similarity analyses were also performed, followed by molecular dynamics and MM-GBSA calculations, to identify potential drugs could be repurposed to combat COVID-19. Indeed, the results suggest that certain terpenoid compounds of plant origin have promising potential as therapeutic targets for SARS-CoV-2. However, additional experimental studies are required to confirm their efficacy as drugs against COVID-19. Communicated by Ramaswamy H. Sarma

Morphological, phytochemical, and transcriptome analyses provide insights into the biosynthesis of monoterpenes in Monarda citriodora.

Morphological, phytochemical, and transcriptome analyses revealed candidate genes involved in the biosynthesis of volatile monoterpenes and development of glandular trichomes in Monarda citriodora. Monarda citriodora Cerv. ex Lag. is a valuable aromatic plant due to the presence of monoterpenes as major constituents in its essential oil (EO). Thus, it is of sheer importance to gain knowledge about the site of the biosynthesis of these terpenoid compounds in M. citriodora, as well as the genes involved in their biosynthesis. In this study, we studied different types of trichomes and their relative densities in three different developmental stages of leaves, early stage of leaf development (L1), mid-stage of leaf development (L2), and later stage of leaf development (L3) and the histochemistry of trichomes for the presence of lipid and terpenoid compounds. Further, the phytochemical analysis of this plant through GC-MS indicated a higher content of monoterpenes (thymol, thymoquinone, γ-terpinene, p-cymene, and carvacrol) in the L1 stage with a substantial decrease in the L3 stage of leaf development. This considerable decrease in the content of monoterpenes was attributed to the decrease in the trichome density from L1 to L3. Further, we developed a de novo transcriptome assembly by carrying out RNA sequencing of different plant parts of M. citriodora. The transcriptome data revealed several putative unigenes involved in the biosynthesis of specialized terpenoid compounds, as well as regulatory genes involved in glandular trichome development. The data generated in the present study build a strong foundation for further improvement of M. citriodora, in terms of quantity and quality of its essential oil, through genetic engineering.