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Genome wide analysis identified 14 OBPs in B. tabaci Asia II-1, of which six are new to science. Phylogenetic analysis traced their diversity and evolutionary lineage among Hemipteran insects. Comparative analysis reclassified the OBP gene families among B. tabaci cryptic species: Asia I, II-1, MEAM1, and MED. The 14 OBPs were clustered on four chromosomes of B. tabaci. RT-qPCR showed high expression of OBP3 and 8 across all body tissues and OBP10 in the abdomen. Molecular docking showed that OBP 3 and 10 had high affinity bonding with different candidate ligands, with binding energies ranging from -5.0 to -7.7 kcal/mol. Competitive fluorescence binding assays revealed that β-caryophyllene and limonene had high binding affinities for OBP3 and 10, with their IC50 values ranging from 9.16 to 14 μmol·L-1 and KD values around 7 to 9 μmol·L-1. Behavioural assays revealed that β-caryophyllene and carvacrol were attractants, β-ocimene and limonene were repellents, and γ-terpinene and β-ocimene were oviposition deterrents to B. tabaci. Functional validation by RNAi demonstrated that OBP3 and OBP10 modulated host recognition of B. tabaci. This study expands our understanding of the genomic landscape of OBPs in B. tabaci, offering scope for developing novel pest control strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Coccidiosis poses a significant threat to the poultry industry, with synthetic antibiotics and disinfectants being the primary tools for control. This study investigated the potential of Piper betle L essential oil (PBEO) as a natural alternative against Eimeria tenella, one of the most pathogenic Eimeria species affecting poultry. Our findings revealed that PBEO exhibits significant anticoccidial effects through two primary mechanisms: (i) oocysticidal activity by disintegrating oocyst walls and (ii) inhibition of the sporulation process. PBEO demonstrated oocysticidal activities ranging from 8.67 to 95.33% across concentrations from 0.04 to 40%. Notably, at 72 h post-incubation, a 0.04% PBEO concentration significantly reduced the number of sporulated oocysts (P ≤ 0.05) to 71.67%, showing effects comparable to those of formalin. PBEO reduced 50% of oocyst sporulation (IC 50 ) in the concentration of 1.31% at 72 h. Gas chromatography-mass spectrometry (GC-MS) identified the primary constituents of PBEO, including eugenol, beta-caryophyllene, and other key compounds, collectively constituting 96% of the oil. This research underscores the potential of PBEO as a natural anticoccidial agent and lays the groundwork for further studies aimed at identifying, isolating, and developing active compounds that may specifically target the sporogony process in coccidian parasites., (© 2024. The Author(s).)

A collection of ring distorted analogue of Nootkatone including 6 CTD (Complex to Diversity) compounds and 9 SAR (Structure Activity Relationship) compounds were synthesized utilizing the carbonyl group as a starting reaction point.

Citrus canker, which is caused by Xanthomonas citri , is a severe disease that affects citrus plants worldwide. This paper aimed to compare, for the first time, the chemical composition and anti- Xanthomonas citri activities of essential oils from Schinus molle fresh and dry leaves (EO-FL and EO-DL, respectively). Anti- X. citri activity of spathulenol, the major constituent of oils, was also evaluated. Activities were screened by the broth microdilution method on 96-well culture plates. Three major constituents were identified in EO-FL and EO-DL by GC-MS and GC-FID: spathulenol, β-caryophyllene and caryophyllene oxide. EO-DL (MIC = 31.25 µg/mL), EO-FL (MIC = 62.5 µg/mL) and spathulenol (MIC = 100 µg/mL) were active against X. citri strains (resistant, tolerant and sensitive to copper). Even though results showed that in vitro potential of EO-FL, EO-DL and spathulenol against X. citri , further in vivo studies are needed to prove their applicability to the biocontrol of citrus canker.

Artemisia annua L. ("Qinghao" in Chinese) is a famous traditional Chinese medicinal herb and has been used to treat malaria and various tumors. Our preliminary screening indicated that the EtOAc extract of A. annua manifested activity against HepG2, Huh7, and SK-Hep-1 cell lines with inhibitory ratios of 53.2%, 52.1%, and 59.6% at 200 μg/mL, respectively. Bioassay-guided isolation of A. annua afforded 14 unusual cadinane-involved sesquiterpenoid dimers, artemannuins A‒N (1-14), of which the structures were elucidated by extensive spectral analyses, ECD calculations, and single-crystal X-ray diffraction. Structurally, these compounds were classified into five different types based on the coupled modes of two monomeric sesquiterpenoids. Among them, compounds 1-9 represented the first examples of sesquiterpenoid dimers formed via the C-3‒C-3' single bond of two 5(4 → 3)-abeo-cadinane sesquiterpenoid monomers, while compounds 13 and 14 were dimers fused by cadinane and humulane sesquiterpenoids via an ester bond. Methylated derivatives of 1, 4, 6, and 8 showed antihepatoma activity against HepG2, Huh7, and SK-Hep-1 cell lines with IC 50 values ranging from 30.5 to 57.2 μM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Leonotis nepetifolia (L.) R. Br. (Lamiaceae) is a naturalised medicinal plant in Brazil known as 'cordão-de-frade', being used in folk medicine for the treatment of a variety of conditions such as infections and inflammations. L. nepetifolia leaf and flower essential oils were isolated by hydrodistillation, and their compounds were identified by GC-MS analysis. The leaf essential oil major constituents were germacrene D (31.5%), and β-caryophyllene (19.2%), while in flower essential oil the main constituents were β-elemene (31.2%), and germacrene D (12.1%). The essential oils were investigated against a broad spectrum of bacteria and fungi using the microdilution method, exhibiting MIC 50 values of 3.93-250 µg mL -1 . Both oils showed excellent antifungal properties, which is a very important finding since most fungi have shown increased resistance to known antifungal agents. According to these results, the essential oils of L. nepetifolia are promising sources of new antimicrobial agents, especially for yeast.

The aim of this study was to determine the activity of common thyme ( Thymus vulgare L.), Greek oregano ( Origanum vulgare L. ssp. hirtum ), and common oregano ( Origanum vulgare L. ssp. vulgare ) essential oils (EOs) against selected phytopathogenic microorganisms in relation to their chemical profile. The EOs were obtained from the herbs of 2-year-old plants cultivated in the organic farming system in a temperate climate in Central Europe. The EOs' composition was determined by GC/MS and GC/FID. The investigated species were represented by the following three chemotypes: 'thymol' for common thyme, 'carvacrol' for Greek oregano, and mixed 'caryophyllene oxide + β-caryophyllene' for common oregano. The antimicrobial activity of the EOs was assessed based on minimum inhibitory concentration (MIC) and minimum bactericidal/fungicidal concentration (MBC/MFC) values. The plant pathogenic bacteria Pseudomonas syringae , Xanthomonas hortorum , Erwinia carotovora , and fungi: Fusarium culmorum , Alternaria alternata , Botrytis cinerea , Epicoccum purpurascens , Cladosporium cladosporioides , Phoma strasseri , and Pythium debaryanum were tested. The EOs revealed a stronger inhibitory effect against fungal growth in comparison to bacterial growth (MIC: 0.016-2 µL/mL for fungi and 0.125-4 µL/mL for bacteria). Common thyme and Greek oregano EOs indicated stronger antimicrobial power than common oregano EO. These results were associated with the chemical profile of the analysed EOs. The growth of examined bacteria and fungi strains (in particular, X. hortorum , F. culmorum , and P. debaryanum ) were negatively correlated with the content of phenolic monoterpenes and monoterpene hydrocarbons. Among the tested strains, P. strasseri turned out to be the most sensitive (MIC 0.016 µL/mL) and E. carotovora the most resistant (MIC 0.250-4 µL/mL) to all investigated EOs.

The first synthesis of chlorine-containing hemiketals, rumphellatins A-C ( 1 - 3 ), previously inaccessible by means of total synthesis, was achieved starting from commercially available (-)-β-caryophyllene oxide ( 7 ). Structures of rumphellatins A ( 1 ) and C ( 3 ) were revised, while structures of rumphellatin B ( 2 ) and intermediate rumphellolide C ( 19 ) were confirmed. The study expands availability of exotic norsesquiterpenoids for profiling their biological activity as well as facilitates the elucidation of biosynthetic pathways of their formation.

The natural aroma compound (+)-nootkatone was obtained in selective conversions of up to 74 mol% from inexpensive (+)-valencene substrate by using a comparatively greener biocatalytic process developed based on modifications of the previously published Firmenich method. Buffer identity and concentration, pH, temperature and downstream work-up procedures were optimized to produce a crude product in which >90 % of (+)-valencene had been converted, with high chemoselectivity observed for (+)-nootkatone production. Interestingly, the biotransformation was carried out efficiently at temperatures as low as 21 ºC. Surprisingly, the best results were obtained when an acidic pH in the range of 3-6 was applied, as compared to the previously published procedure in which it appeared to be necessary to buffer the pH optimally and fixed throughout at 8.5. Furthermore, there was no need to maintain a pure oxygen atmosphere to achieve good (+)-nootkatone yields. Instead, air bubbled continuously at a low rate through the reaction mixture via a submerged glass capillary was sufficient to enable the desired lipoxygenase-catalyzed oxidation reactions to occur efficiently. No valencene epoxide side-products were detected in the organic product extract by a standard GCMS protocol. Only traces of the anticipated corresponding α- and β-nootkatol intermediates were routinely observed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Bracken fern (Pteridium spp.) is a highly problematic plant worldwide due to its toxicity in combination with invasive properties on former farmland, in deforested areas and on disturbed natural habitats. The carcinogenic potential of bracken ferns has caused scientific and public concern for six decades. Its genotoxic effects are linked to illudane-type glycosides (ITGs), their aglycons and derivatives. Ptaquiloside is considered the dominating ITG, but with significant contributions from other ITGs. The present review aims to compile evidence regarding environmental pollution by bracken fern ITGs, in the context of their human and animal health implications. The ITG content in bracken fern exhibits substantial spatial, temporal, and chemotaxonomic variation. Consumption of bracken fern as food is linked to human gastric cancer but also causes urinary bladder cancers in bovines browsing on bracken. Genotoxic metabolites are found in milk and meat from bracken fed animals. ITG exposure may also take place via contaminated water with recent data pointing to concentrations at microgram/L-level following rain events. Airborne ITG-exposure from spores and dust has also been documented. ITGs may synergize with major biological and environmental carcinogens like papillomaviruses and Helicobacter pylori to induce cancer, revealing novel instances of chemical and biological co-carcinogenesis. Thus, the emerging landscape from six decades of bracken research points towards a global environmental problem with increasingly complex health implications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Bemisia tabaci poses a severe threat to plants, and the control of B. tabaci mainly relies on pesticides, which causes more and more rapidly increasing resistance. β-Caryophyllene is a promising ingredient for agricultural pest control, but its feature of poor water solubility need to be improved in practical applications. Nanotechnology can enhance the effectiveness and dispersion of volatile organic compounds (VOCs). In this study, a nanoliposome carrier was constructed by ethanol injection and ultrasonic dispersion method, and β-caryophyllene was wrapped inside it, thus solving the defect of poor solubility of β-caryophyllene. The size of the β-caryophyllene nanoliposomes (C-BT-NPs) was around 200 nm, with the absolute value of the zeta potential exceeding 30 mV and a PDI below 0.5. The stability was also maintained over a 14-d storage period. C-BT-NPs showed effective insecticidal activity against B. tabaci, with an LC 50 of 1.51 g/L, outperforming thiamethoxam and offering efficient agricultural pest control. Furthermore, C-BT-NPs had minimal short-term impact on the growth of tomato plants, indicating that they are safety on plants. Therefore, the VOCs using nanoliposome preparation technology show promise in reducing reliance on conventional pesticides and present new approaches to managing agricultural pests., (Copyright © 2024. Published by Elsevier Inc.)

The essential oil of Blumea eriantha DC. (Asteraceae) herb (leaves and stems) (BEHO) and roots (BERO) was obtained by hydro-distillation and analyzed by GC-FID and GC-MS. The chemical constituents of BEHO and BERO were identified according to their mass spectra and relative retention indices. Fifty-two and thirty-eight compounds were identified, comprising 97.1% and 95.5% of the BEHO and BERO, respectively. The prodigious differences were observed in the major constituents of BEHO and BERO. The major compounds were chrysanthenone (52.8%) and 2,4-dimethylether phloroacetophenone (15.1%) (BEHO), 2,5-dimethoxy- p -cymene (31.3%), epi - α -cadinol (12.7%) and γ -cadinene (10.5%) (BERO). The BEHO found a higher concentration of oxygenated monoterpenes, while BERO with phenyl derivatives type of constituents.

Ferroptosis is a form of regulated cell death triggered by iron-dependent lipid peroxidation and has been associated with heart diseases. However, there are currently no approved drugs that specifically inhibit ferroptosis in clinical practice, which largely limits the translational potential of this novel target. Here, we demonstrated that β-caryophyllene (BCP; 150 μM), a natural dietary cannabinoid, protects cardiomyocytes against ferroptotic cell death induced by cysteine deprivation or glutathione peroxidase 4 (GPX4) inactivation. Moreover, BCP preserved the mitochondrial morphology and function during ferroptosis induction. Unexpectedly, BCP supported ferroptosis resistance independent of canonical antiferroptotic pathways. Our results further suggested that BCP may terminate radical chain reactions through interactions with molecular oxygen, which also explains why its oxidation derivative failed to suppress ferroptosis. Finally, oral BCP administration (50 mg/kg, daily) significantly alleviated doxorubicin (15 mg/kg, single i.p. injection)-induced cardiac ferroptosis and cardiomyopathy in mice. In conclusion, our data revealed the role of BCP as a natural antiferroptotic compound and suggest pharmacological modification based on BCP as a promising therapeutic strategy for treating ferroptosis-associated heart disorders.

Sandalwood essential oil is extracted from the heartwood part of mature sandalwood and is known for its pleasant fragrance and exceptional medicinal activities, including antimicrobial, antitumor, and anti-inflammatory properties. The (Z)-α-santalol and (Z)-β-santalol are the most vital ingredients contributing to sandalwood oil's bioactivities and unique woody odor characteristics. Metabolic engineering strategies have shown promise in transforming microorganisms such as yeast and bacteria into effective cell factories for enhancing the production of vital sesquiterpenes (santalene and santalol) found in sandalwood oil. This review aims to summarize sources of sandalwood oil, its components/ingredients, and its applications. It also highlights the biosynthesis of santalene and santalol and the various metabolic engineering strategies employed to reconstruct and enhance santalene and santalol biosynthesis pathways in heterologous hosts.

To discover novel natural product-based insecticides, a series of (+)-nootkatone-based amine derivatives 3a-t were prepared and evaluated for their insecticidal activities against Mythimna separata Walker, Myzus persicae Sulzer, and Plutella xylostella Linnaeus. Insecticidal assays showed that most of the title (+)-nootkatone derivatives exhibited stronger insecticidal activities against three insect pests than the precursor (+)-nootkatone after the introduction of amine groups on the parent (+)-nootkatone. Compounds 3a , 3d , 3h , 3m , 3n , 3p , and 3r displayed more promising growth inhibitory (GI) effect against M. separata than the commercially available botanical insecticide toosendanin. Compound 3o exhibited the most potent aphicidal activity with an LD 50 value of 0.011 μg/larvae, which was 2.09-fold higher than the positive control rotenone. Additionally, compounds 3g and 3n showed more promising larvicidal activity against P. xylostella with LC 50 values of 260 and 230 mg/L, respectively, superior to that of rotenone (460 mg/L). Moreover, derivatives 3g and 3n exhibited better control efficacy toward P. xylostella than rotenone under greenhouse conditions. Preliminary mechanistic studies revealed that derivative 3n could inhibit the activity of glutathione S -transferase (GST) in P. xylostella and thus exerted larvicidal activity, and molecular docking further demonstrated that 3n could interact well with some amino acid residues of GST. Finally, the toxicity assay suggested that derivatives 3g and 3n were relatively less toxic to nontarget organisms. These findings will provide insights into the development of (+)-nootkatone derivatives as green pesticides.

The natural antimicrobial properties of essential oils (EOs) have contributed to the battle against multidrug-resistant microorganisms by providing new ways to develop more effective antibiotic agents. In this study, we investigated the chemical composition of Ocotea diospyrifolia essential oil (OdOE) and its antimicrobial properties combined with amikacin (AMK). Through gas chromatography-mass spectrometry (GCMS) analysis, the primary constituents of OdOE were identified as α-bisabolol (45.8 %), β-bisabolene (9.4 %), γ-elemene (7.6 %), (Z)- β-farnesene (5.2 %), spathulenol (3.5 %), (Z)-caryophyllene (3.3 %), and (E)-caryophyllene (3.1 %). In vitro assessments showed that the combined administration of OdOE and AMK exerted a synergistic antibacterial effect on the multidrug-resistant K. pneumoniae strain. This synergistic effect demonstrated bacteriostatic action. OdEO combined with amikacin showed protein extravasation within 2 h of treatment, leading to bacterial death, which was determined by a reduction in viable cell count. The effective concentrations showed hemocompatibility. In vivo assessments using Caenorhabditis elegans as a model showed the survival of 85 % of infected nematodes. Therefore, the combination OdEO combined with amikacin exhibited antimicrobial activity against a multidrug-resistant K. pneumoniae strain. Thus, OdOE is a promising agent that may be considered for development of antimicrobial treatment., Competing Interests: Declaration of competing interest We have no conflict of interest to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The genus Knema Lour. is distributed mainly in Southeast Asian and widely used in folk medicine for treating diseases such as jaundice, chronic fever, and inflammation. The chemical composition, acetylcholinesterase inhibition, and molecular docking studies of essential oil from Knema hookeriana Warb. were investigated in this study. The essential oil was achieved through hydrodistillation and was characterised using gas chromatography (GC-FID) and gas chromatography-mass spectrometry (GC-MS). The acetylcholinesterase inhibitory activity was evaluated using Ellman method while molecular docking studies were carried out using Autodock v.4.3.2. The results revealed that the essential oil examined consisted mainly of β-caryophyllene (26.2%), germacrene D (12.5%), δ-cadinene (9.2%), germacrene B (8.8%) and bicyclogermacrene (5.5%). The essential oil showed acetylcholinesterase activity with IC 50 value of 70.5 µg/mL. The enzyme-ligand molecular docking study showed that β-caryophyllene and δ-cadinene exhibited good binding affinities towards AChE with docking scores -8.1 kcal/mol and -8.3 kcal/mol, respectively.

Although rare, amoebic keratitis (AK) is a disease caused by Acanthamoeba spp. that can lead to blindness. The drugs currently available for its treatment are very toxic, which has motivated the investigation for more effective and safe therapeutic options. In this study, the in vitro activity of ß-caryophyllene (BCP) was exploited taking into account its action against other protozoans as well as its well-known healing and anti-inflammatory properties (aspects relevant for the AK pathogenesis). On the other hand, high volatilization and oxidation phenomena are found for this compound, which led to its incorporation into nanoemulsions (NEs). Two emulsifying agents were tested, resulting in monodisperse systems with reduced droplet size (<265 nm) and high surface charge (positive and negative for NEs prepared with cetrimonium bromide -CTAB and Phosal® 50+, respectively). NEs prepared with CTAB were shown to be more stable after long-term storage at 4 and 25 °C than those prepared with Phosal®. Pure BCP, at the highest concentration (500 µM), resulted in a level of inhibition of Acanthamoeba trophozoites equivalent to that of reference drug (chlorhexidine). This activity was even greater after oil nanoencapsulation. The reduced droplet size could improve the interaction of the oil with the microorganism, justifying this finding. Changes in surface charge did not impact the activity. Positively charged NEs improved the interaction and retention of BCP in the cornea and thus should be prioritized for further studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this work, a group of ten sesquiterpene drimanes, including polygodial ( 1 ), isopolygodial ( 2 ), and drimenol ( 3 ) obtained from the bark of Drimys winteri F. and seven synthetic derivatives, were tested in vitro against a unique panel of bacteria, fungi, and oomycetes with standardized procedures against bacterial strains K. pneumoniae , S. tiphy , E. avium , and E. coli. The minimum inhibitory concentrations and bactericidal activities were evaluated using standardized protocols. Polygodial ( 1 ) was the most active compound, with MBC 8 μg/mL and MIC 16 μg/mL in E. avium ; MBC 16 μg/mL and MIC 32 μg/mL in K. pneumoniae ; MBC 64 μg/mL and MIC 64 μg/mL in S. typhi ; and MBC 8 μg/mL and MIC 16 μg/mL and MBC 32 μg/mL and MIC 64 μg/mL in E. coli , respectively. The observed high potency could be attributed to the presence of an aldehyde group at the C8-C9 position. The antifungal activity of 1 from different microbial isolates has been evaluated. The results show that polygodial affects the growth of normal isolates and against filamentous fungi and oomycetes with MFC values ranging from 8 to 64 μg/mL. Sesquiterpene drimanes isolated from this plant have shown interesting antimicrobial properties.

GC/MS analysis of Murraya koenigii (L.) Spreng. and Murraya paniculata (L.) Jacq. leaves revealed the identification of 73 components, with an evident greater contribution of monoterpenes hydrocarbons to their total volatiles. α-Pinene (37.5%) and β-caryophyllene (27.4%) were the most abundant compounds in M. koenigii leaves and β-phellandrene (40.7%) in M. paniculata leaves, using headspace. β-Phellandrene (33.7%) was the major constituent by M. koenigii leaves where germacrene D (23.8%), and δ-elemene (22.0%) were predominant in M. paniculata leaves, using steam distillation. M. koenigii leaves oil showed quite remarkable cholinesterase inhibitory activity, where oil of M. paniculata leaves showed strong inhibitory activity against AChE (IC 50 =13.2 ± 0.9 µg/mL) and BChE (IC 50 =5.1 ± 0.3 µg/mL). Germacrene D, α-zingiberene, and δ-elemene showed higher affinity to BChE than AChE as revealed from docking scores (S = -5.65 to -6.03 Kcal/mol) for BChE and (S = -5.56 to -6.25 Kcal/mol) for AChE.

The present study provides the first information on the chemical composition and acetylcholinesterase inhibitory activity of the essential oil (EO) from the leaves of Mitrephora poilanei Weeras. & R.M.K.Saunders from Vietnam. Gas chromatography and gas chromatography-mass spectrometry analysis revealed that the main components of the M. poilanei EO were β-caryophyllene (13.2%), α-humulene (10.5%), germacrene D (8.1%), β-elemene (5.2%) and bicyclogermacrene (5.1%). The anti-acetylcholinesterase assay showed that the EO displayed moderate activity with IC 50 value of 31.16 ± 3.06 μg/mL. These findings proposed that the plant can be exploited for its anti-acetylcholinestrate potential.

This study aimed to develop a relatively natural and safe botanical insecticide for controlling the storage pest Tribolium castaneum in the egg and pupal stages. It examined how Elsholtzia densa Benth. essential oil (EO) and its primary components, β-caryophyllene and limonene, affected T. castaneum eggs and pupae through contact and fumigation. Among th, the contact activities of β-caryophyllene against T. castaneum eggs and pupae are LD 50 (median lethal dose, 50%) = 0.156 mg/cm 2 and ED 50 (median effective dose, 50%) = 16.35 mg/pupa respectively. The study also investigated the effect of β-caryophyllene and limonene on T. castaneum eggs and pupae through synergistic contact and fumigation. When the mixing ratio of β-caryophyllene and limonene was 7:1, the LD 50 value of contact activity against T. castaneum eggs was reduced to 0.100 mg/cm 2 , displaying an obvious synergistic effect. Experiments were conducted to investigate the antitoxic effect of β-caryophyllene on T. castaneum eggs and pupae, as well as its effects on the enzymatic activity of acetylcholinesterase, succinate dehydrogenase, glutathione S-transferase and carboxylesterase in T. castaneum pupae. Finally, the molecular docking techniques were employed to confirm the aforementioned effects on enzyme function. The findings of this study might help improve storage pest control with T. castaneum and create eco-friendly insecticides using E. densa EO, β-caryophyllene, and limonene., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

The abnormal deposition of tau protein is one of the critical causes of tauopathies including Alzheimer's disease (AD). In recent years, there has been great interest in the use of essential oils and volatile compounds in aromatherapy for treating AD, since volatile compounds can directly reach the brain through intranasal administration. The volatile compounds α-asarone (ASA) and β-caryophyllene (BCP) have revealed various important neuroprotective properties, useful in treating AD. In this study, the volatile compounds ASA and BCP were assessed for their effectiveness in preventing tau fibrillation, disassembly of pre-formed tau fibrils, and disaggregation of tau aggregates. SDS-PAGE and AFM analyses revealed that ASA and BCP inhibited tau fibrillation/aggregation and decreased the mean size of tau oligomers. Tau samples treated with ASA and BCP, showed a reduction in ThT and ANS fluorescence intensities, and a decrease in the β-sheet content. Additionally, ASA and BCP disassembled the pre-formed tau fibrils to the granular and linear oligomeric intermediates. Treatment of neuroblastoma SH-SY5Y cells with tau samples treated with ASA and BCP, revealed protective effects as shown by reduced toxicity of the cells, due to the inhibition of tau fibrillation/aggregation. Overall, ASA and BCP appeared to be promising therapeutic candidates for AD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

New essential oils (EOs) extracted from different parts of two Luvunga species ( L. scandens and L. hongiaoensis ) from Vietnam were investigated for their chemical composition, anti-inflammatory and cytotoxic activity. Sixty-nine total compounds were identified in the EOs by GC/MS. The major constituent of the leaf, fruit, and root EOs from L. scandens was β-caryophyllene (71.5%, 63.0%, and 31.5% respectively). The main compounds in L. hongiaoensis EOs were β-elemene (34.3% in leaf oil) and caryophyllene oxide (21.2% in root oil, 19.4% in stem oil). The EO from L. scandens fruits significantly inhibited nitric oxide production on LPS-induced RAW264.7 cells (IC 50 = 37.95 ± 2.76 µg/mL). The EOs from L. hongiaoensis roots and L. scandens leaves and fruits exhibited cytotoxic activity against MCF-7, SK-LU-1, and HepG2 (IC 50 from 49.74 ± 3.36 to 97.82 ± 8.61 µg/mL). This is the first report on L. hongiaoensis EOs and significantly complements the composition and bioactivity of L. scandens EOs.

Five undescribed eremophilane-type sesquiterpenes, remophilanetriols E-I (1-5), along with seven known compounds (6-12) were isolated from the fresh roots of Rehmannia glutinosa. Their structures were characterized by extensive spectroscopic data analysis and their absolute configurations were determined by comparing their calculated electronic circular dichroism (ECD) spectra and experimental ECD spectra. The anti-pulmonary fibrosis activities of all compounds were evaluated in vitro by MTT methods, and compounds 2, 8, 10, and 12 exhibited excellent anti-pulmonary fibrosis activities. In addition, compound 2 can reduce the levels of ROS and apoptosis in TGF-β1-induced BEAS-2B cells., Competing Interests: Declaration of competing interest No other potential conflict of interest relevant to this article was reported., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In an attempt to search for new natural products-based antifungal agents, fifty-three nootkatone derivatives were designed, synthesized, and evaluated for their antifungal activity against Phytophthora parasitica var nicotianae, Fusarium oxysporum, Fusarium graminearum and Phomopsis sp. by the mycelium growth rate method. Nootkatone derivatives N17 exhibited good inhibitory activity against Phomopsis. sp. with EC 50 values of 2.02 μM. The control effect of N17 against Phomopsis. sp. on kiwifruit showed that N17 exhibited a good curative effect in reducing kiwifruit rot at the concentration of 202 μM(100×EC 50 ), with the curative effect of 41.11 %, which was better than commercial control of pyrimethanil at the concentration of 13437 μM(100×EC 50 ) with the curative effect of 38.65 %. Phomopsis. sp. mycelium treated with N17 showed irregular surface collapse and shrinkage, and the cell membrane crinkled irregularly, vacuoles expanded significantly, mitochondria contracted, and organelles partially swollen by the SEM and TEM detected. Preliminary pharmacological experiments show that N17 exerted antifungal effects by altering release of cellular contents, and altering cell membrane permeability and integrity. The cytotoxicity test demonstrated that N17 showed almost no toxicity to K562 cells. The presented results implied that N17 may be as a potential antifungal agents for developing more efficient fungicides to control Phomopsis sp., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

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.

The bridged polycyclic sesquiterpenoids derived from sativene, isosativene, and longifolene have unique structures, and many chemical synthesis approaches with at least 10 steps have been reported. However, their biosynthetic pathway remains undescribed. A minimal biosynthetic gene cluster (BGC), named bip , encoding a sesquiterpene cyclase (BipA) and a cytochrome P450 (BipB) is characterized to produce such complex sesquiterpenoids with multiple carbon skeletons based on enzymatic assays, heterologous expression, and precursor experiments. BipA is demonstrated as a versatile cyclase with (-)-sativene as the dominant product and (-)-isosativene and (-)-longifolene as minor ones. BipB is capable of hydroxylating different enantiomeric sesquiterpenes, such as (-)-longifolene and (+)-longifolene, at C-15 and C-14 in turn. The C-15- or both C-15- and C-14-hydroxylated products are then further oxidized by unclustered oxidases, resulting in a structurally diverse array of sesquiterpenoids. Bioinformatic analysis reveals the BipB homologues as a discrete clade of fungal sesquiterpene P450s. These findings elucidate the concise and divergent biosynthesis of such intricate bridged polycyclic sesquiterpenoids, offer valuable biocatalysts for biotransformation, and highlight the distinct biosynthetic strategy employed by nature compared to chemical synthesis.

The repellent capacity against Sitophilus zeamais and the in vitro inhibition on AChE of 11 essential oils, isolated from six plants of the northern region of Colombia, were assessed using a modified tunnel-type device and the Ellman colorimetric method, respectively. The results were as follows: (i) the degree of repellency (DR) of the EOs against S. zeamais was 20-68% (2 h) and 28-74% (4 h); (ii) the IC 50 values on AChE were 5-36 µg/mL; likewise, the %inh. on AChE (1 µg/cm 3 per EO) did not show any effect in 91% of the EO tested; (iii) six EOs ( Bursera graveolens -bark, B. graveolens -leaves, B. simaruba -bark, Peperomia pellucida -leaves, Piper holtonii (1b*)-leaves, and P. reticulatum -leaves) exhibited a DR (53-74%) ≥ C + (chlorpyrifos-61%), while all EOs were less active (8-60-fold) on AChE compared to chlorpyrifos (IC 50 of 0.59 µg/mL). Based on the ANOVA/linear regression and multivariate analysis of data, some differences/similarities could be established, as well as identifying the most active EOs (five: B. simaruba -bark, Pep. Pellucida -leaves, P. holtonii (1b*)-leaves, B. graveolens -bark, and B. graveolens -leaves). Finally, these EOs were constituted by spathulenol (24%)/β-selinene (18%)/caryophyllene oxide (10%)- B. simaruba ; carotol (44%)/dillapiole (21%)- Pep. pellucida ; dillapiole (81% confirmed by 1 H-/ 13 C-NMR)- P. holtonii ; mint furanone derivative (14%)/mint furanone (14%)- B. graveolens -bark; limonene (17%)/carvone (10%)- B. graveolens -leaves.

Phenylspirodrimanes (PSD) are the sesquiterpene quinone type meroterpenoids found in nature. PSDs are found to exhibit inhibitory activity against immunocomplex diseases, and tyrosine kinase receptors. Three of the different PSDs C1, C2, and C3 that have been reported to be isolated from the sponge-associated fungus Stachybotrys chartarum MUT 3308 are selected for studying their possible inhibitory effect against type 2 diabetes mellitus. Mechanistically, blocking protein tyrosine phosphatase 1B (PTP1B) helps to reduce the insulin resistance induction caused by the high expression of PTP1B. The QSAR, ADME, toxicity (T) study was carried out to predict the pharmacokinetic properties and the biological activities of the PSDs. PASS prediction web tool was used to find and select the target proteins 1NNY, and 2HNP. According to the molecular docking simulations, C1 and C2 showed better binding affinity of -8.5 kcal/mol, and -8.1 kcal/mol respectively against 1NNY compared to the control ligand. RMSD, RMSF, R g , and SASA analysis revealed that both C1, and C2 showed better stability, minor conformational changes, and minor fluctuation upon binding to PTP1B. Protein contact analysis was carried out to validate the residues that are in contact with the ligands according to molecular docking studies. Overall, C1, and C2 could be proposed as novel natural hits to be developed and small modifications of these PSDs could result in inducing the binding affinity significantly, although experimental validation is required for further evaluation of the work.Communicated by Ramaswamy H. Sarma.

Elucidating the mutual effects between the different volatile organic compounds (VOCs) is crucial for comprehending the formation mechanism of atmospheric secondary organic aerosols (SOA). Here, the mixed VOCs experiments of isoprene and Δ 3 -carene/β-caryophyllene were carried out in the presence of O 3 using an indoor smog chamber. The suppression effect of isoprene was recognized by the scanning mobility particle sizer spectrometer, online vacuum ultraviolet free electron laser (VUV-FEL) photoionization aerosol mass spectrometry, and quantum chemical calculations. The results indicate that the suppression effect of isoprene on the ozonolysis of Δ 3 -carene and β-caryophyllene shows fluctuating and monotonous trends, respectively. The carbon content of the precursor could be the main factor for regulating the strength of the suppression effect. Plausible structures and formation mechanisms of several new products generated from the single VOC precursor and VOC-cross-reaction are proposed, which enrich the category of VOC oxidation products. Meanwhile, a new dimerization mechanism of the RO 2 + R'O 2 reaction is suggested, which offers an intriguing perspective on the gas phase formation process of particle phase accretion products. The present findings provide valuable insights into clarifying the pivotal roles played by isoprene in the interplay between different VOCs and understanding of SOA formation mechanisms of VOC mixtures, especially nearby the emission origins., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2023. Published by Elsevier B.V.)

Five eremophilane sesquiterpenes including three new ones, named paraconions A-C (1-3), were isolated from an endophytic fungus, Paraconiothyrium sp. from Artemisia selengensis. The structures of these new compounds were established based on spectroscopic methods, including nuclear magnetic resonance (NMR), ultraviolet (UV), and infrared (IR) spectroscopy, as well as high resolution electrospray ionization mass spectrometry (HR-ESI-MS). An anti-inflammatory assay indicated that paraconion B (2) inhibited lipopolysaccharide-induced nitric oxide (NO) production in RAW 264.7 cells, with an IC 50 value of 51.7 μM. The compounds discovered in this study will enrich the structural types of secondary metabolites of the endophytic fungus Paraconiothyrium sp., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Eight new cadinane sesquiterpenoids ( 1 - 8 ), along with two known compounds ( 9 and 10 ), were isolated from infected stems of the semi-mangrove plant, Hibiscus tiliaceus . The structures of compounds 1 - 8 were elucidated through the analysis of their 1D and 2D NMR and MS data, and their absolute configurations were determined by comparing their experimental and calculated ECD spectra and by single-crystal X-ray diffraction. The two confused known compounds ( 9 and 10 ) were resolved using single-crystal X-ray crystallography. Compounds 1 - 3 have novel norsesquiterpene carbon skeletons arising from a ring contraction rearrangement. All obtained isolates were evaluated against the HepG2 and Huh7 cell lines, and compounds 1b , 2b , 4 , 6 , and 8 showed cytotoxic activity toward both cell lines, with IC 50 values ranging from 3.5 to 6.8 μM.

Little is known about the immunomodulatory activity of essential oils isolated from Juniperus species. Thus, we isolated essential oils from the cones and leaves of eight juniper species found in Montana and in Kazakhstan, including J. horizontalis , J. scopolorum , J. communis , J. seravschanica , J. sabina , J. pseudosabina , J. pseudosabina subsp. turkestanica , and J. sibirica . We report here the chemical composition and innate immunomodulatory activity of these essential oils. Compositional analysis of the 16 samples of Juniper essential oils revealed similarities and differences between our analyses and those previously reported for essential oils from this species. Our studies represent the first analysis of essential oils isolated from the cones of four of these Juniper species. Several essential oil samples contained high levels of cedrol, which was fairly unique to three Juniper species from Kazakhstan. We found that these essential oils and pure (+)-cedrol induced intracellular Ca 2+ mobilization in human neutrophils. Furthermore, pretreatment of human neutrophils and N -formyl peptide receptor 1 and 2 (FPR1 and FPR2) transfected HL60 cells with these essential oils or (+)-cedrol inhibited agonist-induced Ca 2+ mobilization, suggesting these responses were desensitized by this pretreatment. In support of this conclusion, pretreatment with essential oils from J. seravschanica cones (containing 16.8% cedrol) or pure (+)-cedrol inhibited human neutrophil chemotaxis to N -formyl peptide. Finally, reverse pharmacophore mapping predicted several potential kinase targets for cedrol. Thus, our studies have identified cedrol as a novel neutrophil agonist that can desensitize cells to subsequent stimulation by N -formyl peptide.

This study aimed to develop a rapid, sensitive, and specific LC-tandem mass spectrometry method for the determination of nootkatone in rat plasma. α-Cyperone was chosen as the internal standard (IS). The plasma was processed using a one-step acetonitrile protein precipitation method. Chromatographic separation of nootkatone was achieved on a Phenomenex Kinetex XB-C18 column (2.10 × 50 mm, 2.6 μm) at 35°C with a mobile phase consisting of acetonitrile and water under a gradient elution at a flow rate of 0.35 mL/min. An electrospray ionization source was applied and operated in positive ion and multiple reaction monitoring modes. Nootkatone and IS were quantified using the transitions of m/z 219.200 → 163.110 and m/z 219.200 → 111.000, respectively. The calibration curves were linear over the range of 10-2000 ng/mL (r = 0.9943). The lower limit of quantification was 10 ng/mL. The intra- and inter-day precision (relative standard deviation) ranged from 2.56% to 8.41%, with the accuracy values ranging from 98.9% to 99.17% for four different concentration levels. The matrix effect and extraction recovery were within acceptable limits. The validated method was successfully applied to the pharmacokinetic study of nootkatone in rats after oral and intravenous administration at three dosages. The main pharmacokinetic parameters were calculated, showing low bioavailability of nootkatone., (© 2021 John Wiley & Sons, Ltd.)

Cedrol has been shown to exert anti-tumor, anti-inflammatory, and anti-oxidative effects, but its role in osteoarthritis (OA) is unclear. This study aimed to explore the effect of cedrol in OA. Chondrocytes were isolated from newborn rats and cultured in Dulbecco's modified Eagle's medium (DMEM). Then, Alcian blue staining was used to identify the chondrocytes. IL-1β and cedrol were used to treat chondrocytes. Cell viability and apoptosis were measured by MTT and flow cytometry assays, respectively. The expressions of miR-542-5p, miR-26b-5p, miR-572, miR-138-5p, miR-328-3p, miR-1254, Bcl-2, Bax, iNOS, COX-2, and MMP-13 were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR) or western blot. NO and PGE2 levels were detected by ELISA. All the cells extracted from the newborn rats were dyed blue, indicating that the cells were chondrocytes. IL-1β could reduce the viability and promote apoptosis and inflammatory response of chondrocytes, while cedrol could reverse the effect of IL-1β. In addition, cedrol could significantly increase the expression of miR-542-5p in IL-1β-treated chondrocytes. Moreover, miR-542-5p inhibitor could partly reverse the effect of cedrol in the apoptosis and inflammation response of chondrocytes. Cedrol alleviated IL-1β-induced apoptosis and inflammatory response of chondrocytes by promoting miR-542-5p expression., (© 2021. The Society for In Vitro Biology.)

Many plants show significant biological activity against pests due to their unique chemical constituents. It is important to identify effective constituents for their development and utilization as botanical pesticides. Our previous study showed that Artemisia lavandulaefolia essential oil had biological activity against Plutella xylostella . Here, we isolated and identified the constituents of essential oil from A . lavandulaefolia by silica gel column chromatography. The main constituents identified were eucalyptol and caryophyllene oxide, and they were confirmed by gas chromatography-mass spectrometry (GC-MS). Eucalyptol and caryophyllene oxide showed strong contact toxicity against P. xylostella larvae after 24 h of application (Median lethal dose, LD 50 = 76.97 μL/mL and 20.71 mg/mL. Furthermore, the two active constituents against P. xylostella adults showed significant fumigant activity (Mmedian lethal concentration, LC 50 = 3.25 μL/L and 1.06 mg/L, respectively. Finally, we measured the detoxification enzymes and acetylcholinesterase of the larvae treated with active constituents. The eucalyptol-treated larvae displayed enhanced carboxylesterase (CarE) and glutathione-S-transferase (GST) activities in an in vivo experiment, but it was lower for acetylcholinesterase (AchE) activity. The activities of the CarE and GST significantly decreased when exposed to caryophyllene oxide. In general, the two active constituents, eucalyptol and caryophyllene oxide, showed high insecticidal activity, which demonstrates their potential to be used as natural insecticides.

The present work involves a systematic review of the chemical composition and biological effects of essential oils from the Annonaceae species collected in Brazil from 2011 to 2021. Annonaceae is one of the most important botanical families in Brazil, as some species have economic value in the market as local and international fruit. In addition, the species have useful applications in several areas-for instance, as raw materials for use in cosmetics and perfumery and as medicinal plants. In folk medicine, species such as Annona glabra L. and Xylopia sericea A. St.-Hil. are used to treat diseases such as rheumatism and malaria. The species of Annonaceae are an important source of essential oils and are rich in compounds belonging to the classes of mono and sesquiterpenes; of these compounds, α-pinene, β-pinene, limonene, ( E )-caryophyllene, bicyclogermacrene, caryophyllene oxide, germacrene D, spathulenol, and β-elemene are the most abundant. The antimicrobial, anti-inflammatory, antileishmania, antioxidant, antiproliferative, cytotoxic, larvicidal, trypanocidal, and antimalarial activities of essential oils from the Annonaceae species in Brazil have been described in previous research, with the most studies on this topic being related to their antiproliferative or cytotoxic activities. In some studies, it was observed that the biological activity reported for these essential oils was superior to that of drugs available on the market, as is the case of the essential oil of the species Guatteria punctata (Aubl.) R. A. Howard., which showed a trypanocidal effect that was 34 times stronger than that of the reference drug benznidazol.

Cannabis sativa L. crops have been traditionally exploited as sources of fibers, nutrients, and bioactive phytochemicals of medical interest. In the present study, two terpene-rich organic extracts, namely FOJ and FOS, obtained from Felina 32 hemp inflorescences collected in June and September, respectively, have been studied for their in vitro anticancer properties. Particularly, their cytotoxicity was evaluated in different cancer cell lines, and the possible entourage effect between nonintoxicating phytocannabinoids (cannabidiol and cannabichromene) and caryophyllane sesquiterpenes (β-caryophyllene, β-caryophyllene oxide and α-humulene), as identified at GC/MS analysis, was characterized. Modulation of cannabinoid CB1 and CB2 receptors was studied as a mechanistic hypothesis. Results highlighted marked cytotoxic effects of FOJ, FOS, and pure compounds in triple negative breast cancer MDA-MB-468 cells, likely mediated by a CB2 receptor activation. Cannabidiol was the main cytotoxic constituent, although low levels of caryophyllane sesquiterpenes and cannabichromene induced potentiating effects; the presence in the extracts of unknown antagonistic compounds has been highlighted too. These results suggest an interest in Felina 32 hemp inflorescences as a source of bioactive phytocomplexes with anticancer properties and strengthen the importance of considering the possible involvement of minor terpenes, such as caryophyllane sesquiterpenes, in the entourage effect of hemp-based extracts.

Ten new bisabolane derivatives, trichobisabolins Q-Z (1-10), one new cadinane derivative, cadin-4-en-11-ol (11), and three new cyclonerane derivatives, cycloner-3-en-7,11-diol (12), isoepicyclonerodiol oxide (13), and norepicyclonerodiol oxide (14), were isolated from the endophytic fungal strain RR-dl-6-11 of Trichoderma asperelloides that was obtained from a marine alga. Their structures along with relative configurations were established mainly by NMR and IR as well as MS techniques, and the absolute configurations of 10 and 11 were assigned by ECD and X-ray diffraction data, respectively. Sesquiterpenes from the fungus T. asperelloides are reported for the first time. It is interesting that half of the bisabolane derivatives are demethylated. Compound 12 represents the first the occurrence of cyclopentenyl-bearing cycloneranes, and 14 seems a cyclopentyl-degrading cyclonerane derivative. Several isolates feature potent inhibition of marine phytoplankton species., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aflatoxin B 1 (AFB 1 ) is a mycotoxin highly toxic and carcinogenic to humans due to its potential to induce oxidative stress. The Beta-caryophyllene (BCP) have been highlighted for its broad spectrum of pharmacological effects. The present study aimed to investigate the beneficial effects of BCP against the susceptibility of hepatic and renal tissues to AFB 1 toxicity, in biochemical parameters to assess organ function, tissue oxidation, and the immunocontent of oxidative and inflammatory proteins. Male Wistar rats was exposed to AFB 1 (250 μg/kg, i.g.) and/or BCP (100 mg/kg, i.p.) for 14 successive days. It was found that exposure to AFB 1 did not change the measured renal toxicity parameters. Also, AFB 1 increased liver injury biomarkers (gamma glutamyl transferase and alkaline phosphatase) and reduced levels of non-enzymatic antioxidant defenses (ascorbic acid and non-protein thiol), however did not cause changes in the lipid peroxidation levels. Moreover, AFB 1 interfered in oxidative pathway regulated by Kelch-like ECH-associated protein (Keap1)/nuclear factor (erythroid-derived 2)-like 2 (Nrf2), overacting Glutathione-S-Transferase (GST) activity. Lastly, a main effect of AFB 1 on the total interleukin 1 beta (IL-1β) was observed. Remarkably, the associated treatment of AFB 1  + BCP improved altered liver parameters. In addition, BCP and AFB 1  + BCP groups showed an increase in the levels of inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ). Thus, these results indicated that BCP has potential protective effect against AFB 1 induced hepatotoxicity., (Copyright © 2021. Published by Elsevier B.V.)

Fifteen new highly oxygenated eremophilane sesquiterpenoids, parasubolides A-O (1-15), were obtained from the whole plant of Parasenecio albus. The structures of 1-15 were elucidated based on the interpretation of NMR and HRESIMS data, along with experimental electronic circular dichroism (ECD) and single-crystal X-ray diffraction analysis. Compounds 1-6, and 9-14 represent the first class of 1,2,10-trioxygenated eremophilane lactones. Selected isolates were evaluated for their immunosuppressive activities. Compounds 4, 5, and 12 exhibited moderate inhibition against LPS-induced B-cell proliferation with IC 50 values of 23.1, 33.8, and 26.6 μM, respectively., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Nootkatone, an approved insecticide, is a well-known natural product from grapefruit. A series of fused-thiazole derivatives of nootkatone have been synthesized, and these new compounds were tested against several strains of bacteria. Some of these compounds are found to be potent antimicrobial agents against Staphylococcus aureus and Enterococcus faecium with minimum inhibitory concentration (MIC) values as low as 1.56 μg/mL. The lead compound is bactericidal and very potent against S. aureus persisters. These compounds are nontoxic to human cancer cell lines at 10 μm concentration., (© 2021 Wiley-VCH GmbH.)

The ongoing COVID-19 global pandemic caused by SARS-CoV-2 inspires the development of effective inhibitors to block the SARS-CoV-2 spike-ACE2 interaction. A chemical investigation on the fruiting bodies of Phellinus pini led to the isolation of five aromatic cadinane sesquiterpenoids including four new ones, named piniterpenoids A-D ( 1 - 4 ), as well as three known lignans. Their structures were determined by extensive spectroscopic analysis including HRMS and 1D and 2D NMR. All of the aromatic cadinane sesquiterpenoids inhibited the SARS-CoV-2 spike-ACE2 interaction, with IC 50 values ranging from 64.5 to 99.1 μM. A molecular docking study showed the disruption of the interaction of compound 1 via hydrogen interactions with Arg403, Asp405, and Arg408 of SARS-CoV-2 RBD and Arg393 and His34 residues of ACE2. These results suggested that aromatic cadinane sesquiterpenoids might be useful in developing agents for COVID-19.

A new access to artemisinin is reported based on a selective photochemical hydrothiolation of amorphadiene, a waste product of the industrial semisynthetic route. This study highlights the discovery of two distinctive activation pathways under solvent-free conditions or using a photocatalyst promoting H-abstraction. Subsequently, a chemoselective oxidation of the resulting photochemically generated thioether, followed by a Pummerer rearrangement, affords dihydroartemisinic aldehyde, a key intermediate in the synthesis of artemisinin.

Croton ferrugineus Kunth is an endemic species of Ecuador used in traditional medicine both for wound healing and as an antiseptic. In this study, fresh Croton ferrugineus leaves were collected and subjected to hydrodistillation for extraction of the essential oil. The chemical composition of the essential oil was determined by gas chromatography equipped with a flame ionization detector and gas chromatography coupled to a mass spectrometer using a non-polar and a polar chromatographic column. The antibacterial activity was assayed against three Gram-positive bacteria, one Gram-negative bacterium and one dermatophyte fungus. The radical scavenging properties of the essential oil was evaluated by means of DPPH and ABTS assays. The chemical analysis allowed us to identify thirty-five compounds representing more than 99.95% of the total composition. Aliphatic sesquiterpene hydrocarbon trans-caryophyllene was the main constituent with 20.47 ± 1.25%. Other main compounds were myrcene (11.47 ± 1.56%), β-phellandrene (10.55 ± 0.02%), germacrene D (7.60 ± 0.60%), and α-humulene (5.49 ± 0.38%). The essential oil from Croton ferrugineus presented moderate activity against Candida albicans (ATCC 10231) with an MIC of 1000 μg/mL, a scavenging capacity SC 50 of 901 ± 20 µg/mL with the ABTS method, and very strong antiglucosidase activity with an IC 50 of 146 ± 20 µg/mL.

Propolis is a balsamic product obtained from vegetable resins by exotic Africanized bees Apis mellifera L., transported and processed by them, originating from the activity that explores and maintains these individuals. Because of its vegetable and natural origins, propolis is a complex mixture of different compound classes; among them are the volatile compounds present in the aroma. In this sense, in the present study we evaluated the volatile fraction of propolis present in the aroma obtained by distillation and simultaneous extraction, and its chemical composition was determined using coupled gas chromatography, mass spectrometry, and flame ionization detection. The majority of compounds were sesquiterpene and hydrocarbons, comprising 8.2-22.19% α-copaene and 6.2-21.7% β-caryophyllene, with additional compounds identified in greater concentrations. Multivariate analysis showed that samples collected from one region may have different chemical compositions, which may be related to the location of the resin's production. This may be related to other bee products.

Drimane sesquiterpenoid dialdehydes are natural compounds with antiproliferative properties. Nevertheless, their mode of action has not yet been discovered. Herein, we demonstrate that various drimanes are potent inhibitors of MCL-1 and BCL-xL, two proteins of the BCL-2 family that are overexpressed in various cancers, including lymphoid malignancies. Subtle changes in their structure significantly modified their activity on the target proteins. The two most active compounds are MCL-1 selective and bind in the BH3 binding groove of the protein. Complementary studies by NMR spectroscopy and mass spectrometry analyses, but also synthesis, showed that they covalently inhibit MCL-1 though the formation of a pyrrole adduct. In addition, cytotoxic assays revealed that these two compounds show a cytotoxic selectivity for BL2, a MCL-1/BCL-xL-dependent cell line and induce apoptosis., (© 2021 Wiley-VCH GmbH.)

This work aimed to study the chemical composition, cholinesterase inhibitory activity, and enantiomeric analysis of the essential oil from the aerial parts (leaves and flowers) of the plant Lepechinia paniculata (Kunth) Epling from Ecuador. The essential oil (EO) was obtained through steam distillation. The chemical composition of the oil was evaluated by gas chromatography, coupled to mass spectrometry (GC-MS) and a flame ionization detector (GC-FID). The analyses led to the identification of 69 compounds in total, of which 40 were found in the leaves and 29 were found in the flowers of the plant. The major components found in the oil were 1,8-Cineole, β-Pinene, δ-3-Carene, α-Pinene, ( E )-Caryophyllene, Guaiol, and β-Phellandrene. Flower essential oil showed interesting selective inhibitory activity against both enzymes AChE (28.2 ± 1.8 2 µg/mL) and BuChE (28.8 ± 1.5 µg/mL). By contrast, the EO of the leaves showed moderate mean inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), with IC 50 values of 38.2 ± 2.9 µg/mL and 47.4 ± 2.3 µg/mL, respectively.