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1.
Pestic Biochem Physiol ; 187: 105180, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36127042

RESUMO

Bark beetles rely on detoxifying enzymes to resist the defensive terpenoids of the host tree. Insect cytochrome P450 (CYPs) plays a key role in the detoxification of pesticides and plant allelochemicals. CYP6 family is unique to Insecta, and its biochemical function is basically related to the metabolism of exogenous substances. In this study, we sequenced and characterized the full-length cDNAs of two CYP6 genes from Chinese white pine beetle, Dendroctonus armandi. Spatiotemporal expression profiling revealed that the expression of CYP6CR2 and CYP6DE5 was higher in larval and adult stages of D. armandi than that in other developmental stages, and that two genes predominantly expressed in brain, midgut, fat body, Malpighian tubules or hemolymph. The expression of CYP6CR2 and CYP6DE5 was significantly induced after feeding on the phloem of Pinus armandii and exposure to six stimuli [(±)- α -pinene, (-)-α-pinene, (-)-ß-pinene, (+)-3-carene, (±)-limonene and turpentine]. Importantly, silencing CYP6CR2 and CYP6DE5 separately could increase the sensitivity, led to a significant reduction of the activity of P450, resulting a significant increase in adult mortality after treatment with terpenoids. The comprehensive results of this study showed that in the process of host selection and colonization, the functions of CYPs were mainly to hydrolyze the chemical defense of the host and degrade odor molecules. These findings may help to develop new treatments to control this important pest.


Assuntos
Besouros , Praguicidas , Pinus , Animais , Monoterpenos Bicíclicos , China , Besouros/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Família 6 do Citocromo P450/metabolismo , Limoneno , Monoterpenos/metabolismo , Monoterpenos/farmacologia , Praguicidas/metabolismo , Feromônios/metabolismo , Terpenos , Terebintina/metabolismo
2.
Molecules ; 27(17)2022 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-36080227

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disease associated with memory impairment and other central nervous system (CNS) symptoms. Two myrtenal-adamantane conjugates (MACs) showed excellent CNS potential against Alzheimer's models. Adamantane is a common pharmacophore for drug design, and myrtenal (M) demonstrated neuroprotective effects in our previous studies. The aim of this study is to evaluate the MACs' neuroprotective properties in dementia. METHODS: Scopolamine (Scop) was applied intraperitoneally in Wistar rats for 11 days, simultaneously with MACs or M as a referent, respectively. Brain acetylcholine esterase (AChE) activity, noradrenaline and serotonin levels, and oxidative brain status determination followed behavioral tests on memory abilities. Molecular descriptors and docking analyses for AChE activity center affinity were performed. RESULTS: M derivatives have favorable physicochemical parameters to enter the CNS. Both MACs restored memory damaged by Scop, showing significant AChE-inhibitory activity in the cortex, in contrast to M, supported by the modeling analysis. Moderate antioxidant properties were manifested by glutathione elevation and catalase activity modulation. MACs also altered noradrenaline and serotonin content in the hippocampus. CONCLUSION: For the first time, neuroprotective properties of two MACs in a rat dementia model were observed. They were stronger than the natural M effects, which makes the substances promising candidates for AD treatment.


Assuntos
Adamantano , Doença de Alzheimer , Doenças Neurodegenerativas , Fármacos Neuroprotetores , Acetilcolinesterase/metabolismo , Adamantano/farmacologia , Doença de Alzheimer/tratamento farmacológico , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Monoterpenos Bicíclicos , Aprendizagem em Labirinto , Doenças Neurodegenerativas/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Norepinefrina , Estresse Oxidativo , Ratos , Ratos Wistar , Escopolamina/farmacologia , Serotonina/metabolismo
3.
Molecules ; 27(17)2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36080248

RESUMO

Verbenone and carvone are allylic monoterpenoid ketones with many applications in the fine chemicals industry that can be obtained, respectively, from the allylic oxidation of α-pinene and limonene over a silica-supported iron hexadecachlorinated phthalocyanine (FePcCl16-NH2-SiO2) catalyst and with t-butyl hydroperoxide (TBHP) as oxidant. As there are no reported analyses of the environmental impacts associated with catalytic transformation of terpenes into value-added products that include the steps associated with synthesis of the catalyst and several options of raw materials in the process, this contribution reports the evaluation of the environmental impacts in the conceptual process to produce verbenone and carvone considering two scenarios (SI-raw-oils and SII-purified-oils). The impact categories were evaluated using ReCiPe and IPCC methods implemented in SimaPro 9.3 software. The environmental impacts in the synthesis of the heterogeneous catalyst FePcCl16-NH2-SiO2 showed that the highest burdens in terms of environmental impact come from the use of fossil fuel energy sources and solvents, which primarily affect human health. The most significant environmental impacts associated with carvone and verbenone production are global warming and fine particulate matter formation, with fewer environmental impacts associated with the process that starts directly from turpentine and orange oils (SI-raw-oils) instead of the previously extracted α-pinene and limonene (SII-purified-oils). As TBHP was identified as a hotspot in the production process of verbenone and carvone, it is necessary to choose a more environmentally friendly and energy-efficient oxidizing agent for the oxidation of turpentine and orange oils.


Assuntos
Dióxido de Silício , Terebintina , Monoterpenos Bicíclicos , Monoterpenos Cicloexânicos , Humanos , Limoneno , Óleos Vegetais
4.
Proc Natl Acad Sci U S A ; 119(35): e2209134119, 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-35994653

RESUMO

Many mass spectrometry methods using various ionization sources provide bulk composition of airborne particles, but little is known about the surface species that play a major role in determining their physicochemical properties that impact air quality, climate, and health. The present work shows that the composition of surface layers of atmospherically relevant submicron organic particles can be probed without the use of an external ionization source. Solid dicarboxylic acid particles are used as models, with glutaric acid being the most efficient at generating ions. Coating with small diacids or products from α-pinene ozonolysis demonstrates that ions are ejected from the surface, providing surface molecular characterization of organic particles on the fly. This unique approach provides a path forward for elucidating the role of the surface in determining chemical and physical properties of particles, including heterogeneous reactions, particle growth, water uptake, and interactions with biological systems.


Assuntos
Poluição do Ar , Atmosfera , Espectrometria de Massas , Compostos Orgânicos , Propriedades de Superfície , Aerossóis/análise , Poluição do Ar/análise , Atmosfera/química , Monoterpenos Bicíclicos/química , Clima , Exposição Ambiental , Glutaratos/química , Humanos , Íons/química , Espectrometria de Massas/métodos , Compostos Orgânicos/análise , Compostos Orgânicos/química , Ozônio/química , Tamanho da Partícula , Água/química
5.
Chem Commun (Camb) ; 58(71): 9910-9913, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35979664

RESUMO

Structural characterization of the complex [B(ß-pinane)3] (1) reveals non-covalent H⋯H contacts that are consistent with the generation of London dispersion energies involving the ß-pinane ligand frameworks. The homolytic fragmentations of 1, and camphane and sabinane analogues ([B(camphane)3] (2) and [B(sabinane)3] (3)) were studied computationally. Isodesmic exchange results showed that London dispersion interactions are highly dependent on the terpene's stereochemistry, with the ß-pinane framework providing the greatest dispersion free energy (ΔG = -7.9 kcal mol-1) with Grimme's dispersion correction (D3BJ) employed. PMe3 was used to coordinate to [B(ß-pinane)3], giving the complex [Me3P-B(ß-pinane)3] (4), which displayed a dynamic coordination equilibrium in solution. The association process was found to be slightly endergonic at 302 K (ΔG = +0.29 kcal mol-1).


Assuntos
Boranos , Monoterpenos Bicíclicos , Canfanos , Ligantes , Terpenos
6.
Sci Total Environ ; 848: 157494, 2022 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-35914590

RESUMO

Highly oxygenated organic molecules (HOM) formed by the autoxidation of α-pinene initiated by OH radicals play an important role in new particle formation. It is believed that the accretion products, ROOR´, formed by the self- and cross-reaction of peroxy radicals (RO2 + R'O2 reactions), have extremely low volatility and are more likely to participate in nucleation. However, the mechanism of ROOR´ formation has not been fully demonstrated by experiment or theoretical calculation. Herein, we propose a novel mechanism of RO2 reacting with α-pinene (RO2 + α-pinene reactions) that have much lower potential barriers and larger rate constants than the reaction of RO2 with R'O2, which explains the ROOR´ formation found in the mass spectrometry experiments. The ROOR´ resulting from the reaction of RO2 with α-pinene can produce HOM dimers and trimers with a higher oxygen-to­carbon (O/C) ratio through a autoxidation chain. We also demonstrated that the presence of NOx and HO2 radical will reduce the RO2 concentration, but cannot completely inhibit the formation of HOM monomers and ROOR´. Even if one or both of RO2 radicals are acyl peroxy radicals (RC(O)O2), the potential barriers of the reactions between RC(O)O2 and α-pinene (RC(O)O2 + α-pinene reactions) are lower than that of RO2 reacting with RC(O)O2 (RO2 + RC(O)O2 reactions) or RC(O)O2 self-reactions (RC(O)O2 + RC(O)O2 reactions). The current work revealed, for the first time, a mechanism of RO2/RC(O)O2 reacting with α-pinene in the atmosphere, which provides new insight into the atmospheric chemistry of accretion products as SOA precursors.


Assuntos
Atmosfera , Oxigênio , Atmosfera/química , Monoterpenos Bicíclicos , Carbono , Oxigênio/química
7.
J Phys Chem A ; 126(30): 5040-5049, 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35862553

RESUMO

Highly oxygenated organic molecules (HOMs) are important sources of atmospheric aerosols. Resolving the molecular-level formation mechanisms of these HOMs from freshly emitted hydrocarbons improves the understanding of aerosol properties and their influence on the climate. In this study, we measure the electrical mobility and mass-to-charge ratio of α-pinene oxidation products using a secondary electrospray-differential mobility analyzer-mass spectrometer (SESI-DMA-MS). The mass-mobility spectrum of the oxidation products is measured with seven different reagent ions generated by the electrospray. We analyzed the mobility-mass spectra of the oxidation products C9-10H14-18O2-6. Our results show that acetate and chloride yield the highest charging efficiencies. Analysis of the mobility spectra suggests that the clusters have 1-5 isomeric structures (i.e., ion-molecule cluster structures with distinct mobilities), and the number is affected by the reagent ion. Most of the isomers are likely cluster isomers originating from binding of the reagent ion to different sites of the molecule. By comparing the number of observed isomers and measured mobilities and collision cross sections between standard pinanediol and pinonic acid to the values observed for C10H18O2 and C10H16O3 produced from oxidation of α-pinene, we confirm that pinanediol and pinonic acid are the only isomers for these elemental compositions in our experimental conditions. Our study shows that the SESI-DMA-MS produces new information from the first steps of oxidation of α-pinene.


Assuntos
Poluentes Atmosféricos , Ozônio , Aerossóis/química , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/química , Monoterpenos Bicíclicos , Íons , Monoterpenos/análise , Monoterpenos/química , Ozônio/química
8.
Int J Food Microbiol ; 379: 109846, 2022 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-35908494

RESUMO

Pseudomonas fragi is primarily responsible for the spoilage of various foods, especially meat. The aim of this study was to investigate the antibacterial mechanism of 3-carene against P. fragi. 3-Carene treatment decreased the phospholipid content and the fluidity of the cell membrane, induced reactive oxygen species (ROS) generation and affected respiratory chain dehydrogenase, oxoglutarate dehydrogenase and citrate synthase in P. fragi. Metabolomics and proteomics analyses further showed that in the presence of 3-carene, 519 proteins, 136 metabolites in positive ion mode and 100 metabolites in negative ion mode were differentially expressed. These proteins and metabolites were primarily involved in amino acid metabolism, fatty acid degradation, the tricarboxylic acid cycle (TCA cycle) and other processes. Consequently, the stimulation of 3-carene altered cell membrane properties, disturbed important amino acid and energy metabolism, and even caused oxidative stress. Additionally, the results of total viable counts and the total volatile base nitrogen indicated that 3-carene could significantly improve the preservation of refrigerated pork. This study suggested that 3-carene has promising potential to be developed as a food preservative.


Assuntos
Carne de Porco , Pseudomonas fragi , Carne Vermelha , Aminoácidos/metabolismo , Animais , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Monoterpenos Bicíclicos , Metabolômica , Proteômica , Pseudomonas fragi/metabolismo , Carne Vermelha/microbiologia , Suínos
9.
J Phys Chem A ; 126(25): 4068-4079, 2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-35709385

RESUMO

Organonitrates (ON) are important components of secondary organic aerosols (SOAs). α-Pinene (C10H16), the most abundant monoterpene in the troposphere, is a precursor for the formation of several of these compounds. ON from α-pinene can be produced in the gas phase via photochemical processes and/or following reactions with oxidizers including hydroxyl radical and ozone. Gas-phase nitrogen oxides (NO2, NO3) are N sources for ON formation. Although gas-phase reactions of α-pinene that yield ON are fairly well understood, little is known about their formation through heterogeneous and multiphase pathways. In the current study, surface reactions of α-pinene with nitrogen oxides on hematite (α-Fe2O3) and kaolinite (SiO2Al2O3(OH)4) surfaces, common components of mineral dust, have been investigated. α-Pinene oxidizes upon adsorption on kaolinite, forming pinonaldehyde, which then dimerizes on the surface. Furthermore, α-pinene is shown to react with adsorbed nitrate species on these mineral surfaces producing multiple ON and other oxidation products. Additionally, gas-phase oxidation products of α-pinene on mineral surfaces are shown to more strongly adsorb on the surface compared to α-pinene. Overall, this study reveals the complexity of reactions of prevalent organic compounds such as α-pinene with adsorbed nitrate and nitrogen dioxide, revealing new heterogeneous reaction pathways for SOA formation that is mineralogy specific.


Assuntos
Poluentes Atmosféricos , Nitratos , Aerossóis/química , Poluentes Atmosféricos/química , Monoterpenos Bicíclicos , Caulim , Minerais , Monoterpenos/química , Nitratos/química
11.
Biotechnol Lett ; 44(7): 867-878, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35723788

RESUMO

Monoterpenes, such as beta-pinene, are secondary metabolites widely used in the flavors and fragrance industries and can have their structure altered to enhance their applicability, such as producing epoxides, which are used as intermediaries for pharmaceuticals. Epoxides are commonly synthesized by the use of inorganic acids as catalysts, although the acid medium induces epoxide degradation. To overcome these limitations biocatalysis is shown as an alternative. Related to, this work aimed to perform the synthesis of ß-Pinene epoxide using Pseudozyma antarctica lipase B (Novozym®435) as a biocatalyst, while determining the independent variables that influence the reaction using experimental design tools. Different solvent systems were evaluated (cyclohexane, acetonitrile, ethyl acetate, and dichloromethane) until 72 h reaction time, from which ethyl acetate showed higher conversion into the epoxidized product (40% in 24 h). Under the other solvents systems, several oxidized by-products were obtained, such as ketones and aldehydes. Moreover, applying metrics of green chemistry, ethyl acetate was also corroborated as the most promising solvent, with a higher atom economy (66.8%) in comparison to the others (41.3%), and a smaller E-value (1.19). Ethyl acetate was the solvent/acyl donor of choice and had the molar ratio and percentage of biocatalyst increased, which resulted in 80% of the product after 3 h of reaction. To obtain an optimized model, four independent variables (temperature, stirring, molar ratio, percentage of biocatalyst) were evaluated using experimental design tools, Fractional Factorial Design and Central Composite Rotatable Design, with conversions ranging from 23 to 95% after 3 h. All the independent variables were statistically significant (p < 0.05) and had different degrees of impact on the conversion. Kinetic parameters of the reaction were determined using the Lineweaver-Burk model (results under 30.1 mmol for Km and 10.7 mmol.min-1 for Vmax). In conclusion, the combination of two different tools of experimental design provided the development of an optimized model for beta-Pinene epoxidation, achieving high conversion to the epoxidized product after 3 h.


Assuntos
Enzimas Imobilizadas , Compostos de Epóxi , Monoterpenos Bicíclicos , Biocatálise , Enzimas Imobilizadas/metabolismo , Solventes/química
12.
Biomed Res Int ; 2022: 8217380, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35663042

RESUMO

The increasing rates of antimicrobial resistance have demanded the development of new drugs as conventional antibiotics have become significantly less effective. Evidence has identified a variety of phytocompounds with the potential to be used in the combat of infections caused by multidrug-resistant (MDR) bacteria. Considering the verification that terpenes are promising antibacterial compounds, the present research aimed to evaluate the antibacterial and antibiotic-modulating activity of (+)-α-pinene and (-)-borneol against MDR bacterial strains. The broth microdilution method was used to determine the minimum inhibitory concentration (MIC) of the compounds and antibiotics and further evaluate the intrinsic and associated antibiotic activity. These analyses revealed that (+)-α-pinene showed significant antibacterial activity only against E. coli (MIC = 512 µg.mL-1), while no significant inhibition of S. aureus and P. aeruginosa growth was observed (MIC ≥ 1024 µg mL-1). However, when combined with antibiotics, this compound induced a significant improvement in the activity of conventional antibiotics, as observed for ciprofloxacin, amikacin, and gentamicin against Staphylococcus aureus, as well as for amikacin and gentamicin against Escherichia coli, and amikacin against Pseudomonas aeruginosa. On the other hand, (-)-borneol was found to inhibit the growth of E. coli and enhance the antibiotic activity of ciprofloxacin and gentamicin against S. aureus. The present findings indicate that (+)-α-pinene and (-)-borneol are phytocompounds with the potential to be used in the combat of antibacterial resistance.


Assuntos
Antibacterianos , Staphylococcus aureus , Amicacina/farmacologia , Antibacterianos/farmacologia , Monoterpenos Bicíclicos , Canfanos , Ciprofloxacina/farmacologia , Escherichia coli , Gentamicinas/farmacologia , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa
13.
Biotechnol Bioeng ; 119(9): 2574-2589, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35707929

RESUMO

Simvastatin (SIM)-loaded and human decellularized adipose tissue (DAT)-coated porous hydroxyapatite (HAp) microspheres were developed for the first time to investigate their potential on bone regeneration. Microspheres were loaded with SIM and then coated with DAT for modifying SIM release and improving their biological response. HAp microspheres were prepared by water-in-oil emulsion method using camphene (C10 H16 ) as porogen followed by camphene removal by freeze-drying and sintering at 1200°C for 3 h. Sintered HAp microspheres with an average particle size of ~400 µm were porous and spherical in shape. Microspheres were incubated with 1, 2.5, and 5 mg/ml SIM stock solutions for drug loading, and drug loading was determined as 7.5 ± 0.79, 20.41 ± 1.93, and 46.26 ± 0.29 µg SIM/mg microspheres, respectively. SIM loading increased with the increase of the initial SIM loading amount. Faster SIM release was observed in DAT-coated microspheres compared to bare counterparts. Higher SaoS-2 cell attachment and proliferation were observed on DAT-coated microspheres. Significantly higher alkaline phosphatase activity of SaoS-2 cells was observed on DAT-coated microspheres containing 0.01 mg/ml SIM than all other groups (p < 0.01). DAT-coated microspheres loaded with SIM at low doses hold promise for bone tissue engineering applications.


Assuntos
Durapatita , Sinvastatina , Tecido Adiposo , Monoterpenos Bicíclicos , Regeneração Óssea , Humanos , Microesferas , Sinvastatina/farmacologia , Tecidos Suporte
14.
Chirality ; 34(9): 1197-1208, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35670135

RESUMO

Theoretical calculations of optical rotation (OR), although important to predict absolute configurations (ACs) and corroborate experiments, require efficient methodology able to reproduce enantiomer specificity and real OR values. Also, troublesome molecules are recurring in the literature, such as (S)-methyloxirane and (1R,5R)-ß-pinene. This study evaluates DFT functionals B3LYP, CAM-B3LYP, ωB97X-D, M06-2X, and PBE0 considering basis sets aug-cc-pVDZ, aug-cc-pVTZ, 6-311++G(2d,p), and 6-311++G(3df,2p) in OR prediction of 42 rigid organic molecules assessing cases with wrong enantiomeric determination comparing to available experimental data at wavelengths 355, 589, and 633 nm. Functionals CAM-B3LYP and ωB97X-D with aug-cc-pVTZ are indicated here to reproduce experimental values more accurately considering fewer number of wrong AC predictions, normalized RMSD values below 0.70, and a good approximation to experimental values in hierarchical cluster analysis. Methyloxirane AC was reproduced in CAM-B3LYP and PBE0, with [ α ] 355 = 6 . 94 for CAM-B3LYP/aug-cc-pVTZ close to experimental value [ α ] 355 = 7 . 49 ± 0 . 30 . Good results were found for AC of ß-pinene in M06-2X, CAM-B3LYP, and ωB97X-D while the latter in 6-311++G(3df,2p) obtained OR values of [ α ] 589 = 3 . 44 and [ α ] 689 = 4 . 20 close to experimental values [ α ] 589 = 2 . 8 and [ α ] 689 = 4 . 66 ± 0 . 60 . The two molecules aforementioned are, for the first time, reported to give valid theoretical OR values in such simple methodologies. OR calculations were all performed after geometry optimization at the same level of theory, and analysis of different functional combinations for each step in ß-pinene showed it can interfere with AC prediction even in rigid molecules.


Assuntos
Compostos de Epóxi , Monoterpenos Bicíclicos , Rotação Ocular , Estereoisomerismo
15.
J Integr Med ; 20(5): 463-472, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35752587

RESUMO

OBJECTIVE: "Multi-targeting" drugs can prove fruitful to combat drug-resistance of multifactorial disease-cervical cancer. This study envisioned to reveal if Thuja homeopathic mother tincture (MT) and its bioactive component could combat human papillomavirus (HPV)-16-infected SiHa cervical cancer cells since it is globally acclaimed for HPV-mediated warts. METHODS: Thuja MT was studied for its antiproliferative and antimigratory properties in SiHa cells followed by microscopic determination of reactive oxygen species (ROS) generation by 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) staining and loss in mitochondrial membrane potential (MtMP) by rhodamine 123 (Rh123) staining. Apoptosis and autophagy inductions were studied by acridine orange/ethidium bromide (AO/EB) staining and immunoblot analyses of marker proteins. The bioactive component of Thuja MT detected by gas chromatography-mass spectrometry was studied for antiproliferative and antimigratory properties along with in silico prediction of its cellular targets by molecular docking and oral drug forming competency. RESULTS: Thuja MT showed significant antiproliferative and antimigratory potential in SiHa cells at a 50% inhibitory concentration (IC50) of 17.3 µL/mL. An increase in DCFDA fluorescence and loss in Rh123 fluorescence prove that Thuja MT acted through the burst of ROS and loss in MtMP respectively. AO/EB-stained cells under the microscope and immunoblot analyses supported Thuja-induced cellular demise via dual pathways-apoptosis and autophagy. Immunoblots showed cleavage of caspase-3 and poly(adenosine diphosphate-ribose) polymerase-1 (PARP-1) along with upregulation of Beclin-1, microtubule-associated protein 1 light chain 3B (LC3B)-II, and p62 proteins. Hence, the apoptotic cascade followed a caspase-3-dependent pathway supported by PARP-1 cleavage, while autophagic death was Beclin-1-dependent and mediated by accumulation of LC3BII and p62 proteins. Thujone, detected as the bioactive principle of Thuja MT, showed greater anti-proliferative and anti-migratory potential at an IC50 of 77 µg/mL, along with excellent oral drug competency with the ability for gastrointestinal absorption and blood-brain-barrier permeation with nil toxicity. Molecular docking depicted thujone with the strongest affinity for mammalian target of rapamycin, phosphoinositide 3-kinase, and protein kinase B followed by B-cell lymphoma 2, murine double minute 2 and adenosine monophosphate-activated protein kinase, which might act as upstream triggers of apoptotic-autophagic crosstalk. CONCLUSION: Robust "multi-targeting" anticancer potential of Thuja drug and thujone for HPV-infected cervical cancer ascertained its therapeutic efficacy for HPV infections.


Assuntos
Infecções por Papillomavirus , Thuja , Neoplasias do Colo do Útero , Animais , Apoptose , Autofagia , Proteína Beclina-1/farmacologia , Monoterpenos Bicíclicos , Caspase 3 , Linhagem Celular Tumoral , Feminino , Humanos , Mamíferos/metabolismo , Camundongos , Simulação de Acoplamento Molecular , Infecções por Papillomavirus/tratamento farmacológico , Fosfatidilinositol 3-Quinases , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Thuja/química , Thuja/metabolismo , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia
16.
Molecules ; 27(9)2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35565963

RESUMO

Tagetes parryi is a plant empirically used to treat gastrointestinal and inflammatory diseases, its essential oil (EOTP) was obtained from the aerial parts, and the composition was elucidated by GC-MS. The in vivo and in vitro anti-inflammatory activities and the antinociceptive activity of EOTP and (1S)-(-)-verbenone (VERB) were assessed. The major compounds identified for EOTP were verbenone (33.39%), dihydrotagetone (26.88%), and tagetone (20.8%). EOTP and VERB diminished the ear oedema induced with TPA by 93.77 % and 81.13 %, respectively. EOTP and VERB decreased inflammation in a 12-O-tetradecanoylphorbol-13-acetate (TPA) chronic model with ED50 = 54.95 mg/kg and 45.24 mg/kg, respectively. EOTP (15 µg/mL) inhibited the in vitro production of the pro-inflammatory mediators NO (67.02%), TNF-α (69.21%), and IL-6 (58.44%) in LPS-stimulated macrophages. In the acetic induced writhing test, EOTP and VERB showed antinociceptive effects with ED50 = 84.93 mg/kg and ED50 = 45.24 mg/kg, respectively. In phase 1 of the formalin test, EOTP and VERB showed no antinociceptive effects, whereas in phase 2, EOTP (ED50 = 35.45 mg/kg) and VERB (ED50 = 24.84 mg/kg) showed antinociceptive effects. The antinociceptive actions of ETOP and VERB were blocked with the co-administration of L-NAME. This study suggests that EOTP and VERB might be used in the treatment of pain and inflammatory problems.


Assuntos
Asteraceae , Óleos Voláteis , Tagetes , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Monoterpenos Bicíclicos , Edema/induzido quimicamente , Edema/tratamento farmacológico , Óleos Voláteis/farmacologia , Óleos Voláteis/uso terapêutico , Extratos Vegetais/farmacologia
18.
J Chem Phys ; 156(12): 124301, 2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35364892

RESUMO

The conformational landscape of myrtenol (2-pinen-10-ol) and its robustness upon hydration were investigated theoretically and experimentally by employing a synergic combination of quantum chemical calculations and Fourier transform microwave spectroscopy coupled to a supersonic jet expansion. Relaxed potential energy surfaces have been carried out, and the lowest energy conformers of the monomer were found to be associated with different geometries of the hydroxymethyl group from those previously reported [Sedo et al., J. Mol. Spectrosc. 356, 32 (2019)]. Geometry optimizations and harmonic vibrational frequency calculations allowed characterization of the equilibrium structure of the possible conformers of myrtenol. Among the nine predicted structures, four have been observed, analyzed, and identified. The controversy on the geometry was solved with the deuteration of the hydroxyl group, which led to the determination of substitution (rs) geometry, in agreement with the present theoretical results. Interestingly, the four observed conformers exhibit the same orientation of OH as in the allyl alcohol molecule. Furthermore, hydrogen bonding linking myrtenol to water was studied. One monohydrate has been observed and identified. Non-covalent interactions and natural bond orbital analysis were performed to depict the interactions responsible for the stabilization of the observed structure. We conclude that the structure of the hydroxymethyl group is robust and does not change upon hydration.


Assuntos
Água , Monoterpenos Bicíclicos , Ligação de Hidrogênio , Conformação Molecular , Água/química
19.
Xenobiotica ; 52(3): 301-311, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35473450

RESUMO

α-Pinene caused a concentration-responsive increase in bladder hyperplasia and decrease in sperm counts in rodents following inhalation exposure. Additionally, it formed a prospective reactive metabolite, α-pinene oxide.To provide human relevant context for data generated in animal models and explore potential mechanism, we undertook studies to investigate the metabolism of α-pinene to α-pinene oxide and mutagenicity of α-pinene and α-pinene oxide.α-Pinene oxide was formed in rat and human microsomes and hepatocytes with some species differences. Based on area under the concentration versus time curves, the formation of α-pinene oxide was up to 4-fold higher in rats than in humans.While rat microsomes cleared α-pinene oxide faster than human microsomes, the clearance of α-pinene oxide in hepatocytes was similar between species.α-Pinene was not mutagenic with or without induced rat liver S9 in Salmonella typhimurium or Escherichia coli when tested up to 10 000 µg/plate while α-pinene oxide was mutagenic at ≥25 µg/plate.α-Pinene was metabolised to α-pinene oxide under the conditions of the bacterial mutation assay although the concentration was approximately 3-fold lower than the lowest α-pinene oxide concentration that was positive in the assay, potentially explaining the lack of mutagenicity observed with α-pinene.


Assuntos
Poluentes Atmosféricos , Poluentes Atmosféricos/toxicidade , Animais , Monoterpenos Bicíclicos , Dano ao DNA , Masculino , Microssomos Hepáticos/metabolismo , Testes de Mutagenicidade , Mutagênicos/metabolismo , Mutagênicos/farmacologia , Estudos Prospectivos , Ratos
20.
Pest Manag Sci ; 78(8): 3277-3286, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35484724

RESUMO

BACKGROUND: Nanopesticides have been proved to be a powerful and promising tool to solve the issues in agriculture. The purpose of the present study was to develop ecofriendly nanopesticide systems by the strategy of comprehensive utilization of two natural biomass resources (bagasse and turpentine oil) because of their incomparable advantages. RESULTS: In this research, a series of nanocellulose carriers ETOCN-1-ETOCN-4 (ETOCN, esterified TEMPO-oxidized cellulose nanofibers) with different degrees of substitution were prepared and characterized by Fourier-transform infrared (FTIR), X-ray diffraction (XRD) and transmission electron microscopy (TEM). Then, 21 1,3,4-thiadiazole-amide compounds 8a-8u containing gem-dimethylcyclopropane ring were designed, synthesized and characterized. A preliminary bioassay indicated that compound 8i (R = p-Br Ph) exhibited broad-spectrum antifungal activity against the tested fungi. Furthermore, drug-loading complexes 8i/ETOCN-1-8i/ETOCN-4 were fabricated by integration of nanocellulose-based carriers ETOCN-1-ETOCN-4 with bioactive compound 8i, and the drug-loading capacities, microstructures and sustained-releasing performance of these complexes were also investigated. According to the observation of scanning electron microscopy (SEM) images of complex 8i/ETOCN-2, the small-molecule drug and the carrier formed a well-distributed and compact complex, which led to the excellent drug-loading capacity and sustained-releasing performance in the ethanol/water (1:1, v/v) system. CONCLUSIONS: Complexes 8i/ETOCN-1-8i/ETOCN-4 deserved further study as the promising candidates for the development of nanopesticides. © 2022 Society of Chemical Industry.


Assuntos
Amidas , Antifúngicos , Antifúngicos/farmacologia , Monoterpenos Bicíclicos , Espectroscopia de Infravermelho com Transformada de Fourier , Tiadiazóis , Difração de Raios X
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