RESUMEN

BACKGROUND: Triple-negative BC is the most aggressive type of breast cancer and its lack of responsiveness to conventional therapies requires screening of new chemical entities. Anti-migratory compounds are promising to treat metastatic cancer since they inhibit one of the main steps of the metastatic cascade. Spirocyclic compounds are non-conventional structures used as building blocks for the synthesis of biologically active molecules and considered interesting structures in the search for new targets in cancer research. OBJECTIVE: Here, we evaluated the potential of eight synthetic spirocyclohexadienones as cell migration inhibitors. METHODS: The anti-migratory ability of compounds was tested by wound healing and Boyden chamber approaches. Experiments in tubulin were performed by fluorescence and tubulin polymerization techniques. Finally, compounds were submitted to cell proliferation inhibition and flow cytometry assays to explore the mechanism by which they inhibit cell migration. RESULTS: Four compounds inhibited cell migration significantly. Analogs containing the 3,4,5-trimethoxyphenil ring at R1 position were the most potent and, thus, selected for additional experiments. Tubulin polymerization and fluorescence assays highlighted a possible binding of spirocyclohexadienones in the colchicine binding site; however, these compounds did not affect the cell cycle to the same extent as colchicine. Cell proliferation was affected and, notably, the most potent analogs induced apoptosis of tumor cells, suggesting a different mechanism by which they inhibit cell migration. CONCLUSION: We presented, for the first time, a series of eight synthetic spirocyclohexadienones with the ability to inhibit TNBC cell migration. These compounds represent a new category to be explored as anticancer agents.

Asunto(s)

Antineoplásicos/farmacología , Ciclohexenos/farmacología , Compuestos de Espiro/farmacología , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Moduladores de Tubulina/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Ciclohexenos/síntesis química , Ciclohexenos/química , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Estructura Molecular , Polimerizacion/efectos de los fármacos , Compuestos de Espiro/síntesis química , Compuestos de Espiro/química , Neoplasias de la Mama Triple Negativas/patología , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/síntesis química , Moduladores de Tubulina/química

RESUMEN

Many natural phyto-products as perezone (Per) exhibit anti-cancer activities. Using experimental and computational studies, it was described that Poly ADP-ribose polymerase 1(PARP-1) inhibition and the induction of oxidative stress state explain the pro-apoptotic activity of Per. The aim of this study was to evaluate two phyto-products related to Per as anti-cancer agents: hydroxyperezone (OHPer) and its monoangelate (OHPer-MAng). These molecules were structurally characterized employing thermal analysis, IR spectrophotometry and X-ray diffraction techniques. The phyto-compounds evaluated in vitro in six cancer cell lines (K562, MCF-7, MDA-MB-231, HeLa, U373, A549) and non-malignant cells determinate their cytotoxicity, type of induced cell death, ability to avoid cell migration and changes at the redox status of the cell. Using, in vitro and computational studies provided the inhibition of PARP-1 and its potential binding mode. Cell proliferation assays demonstrated that OHPer-MAng treatment significantly induces apoptosis in triple negative breast cancer (TNBC) cell line (MDA-MB-231 IC50 = 3.53 µM), being particularly less cytotoxic to Vero cells (IC50 = 313.92 µM), human lymphocytes (IC50 = 221.46 µM) and rat endothelial cells (IC50=> 400 µM). The treatment of MDA-MB-231 cells with OHPer-MAng showed inhibition of migration by cancer cells. The induction of an oxidative stress state, similar to other quinones and PARP-1 inhibition explains the pro-apoptotic activity of OHPer-MAng. Docking studies showed that OHPer-MAng establishes great non-bonding interactions with the lateral chains of Tyr235, Hys201, Tyr246, Ser203, Asn207, and Gly233 located at the catalytic site of PARP-1, also demonstrating the anti-cancer activity of OHPer-MAng in TNBC cell line.

Asunto(s)

Antineoplásicos/farmacología , Asteraceae/química , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ciclohexenos/farmacología , Extractos Vegetales/farmacología , Sesquiterpenos/farmacología , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Chlorocebus aethiops , Ciclohexenos/química , Células Endoteliales , Humanos , Ratas , Sesquiterpenos/química , Células Vero

RESUMEN

The use in folk medicine of Baccharis trimera and recent studies on DNA damage by oxidative stress mechanisms have motivated this study. We investigated the biotoxicological effects of trimeroside from this plant. Aqueous extract from aerial parts of B. trimera was fractioned by flash chromatography for further isolation by thin-layer chromatography. The novel nor-monoterpene glycoside, trimeroside, and three flavonoids, cirsimaritin, luteolin and quercetin, were isolated. The genotoxic and mutagenic potential of trimeroside was determined by Salmonella/microsome (TA98 and TA100), comet assay, and cytokinesis-block micronucleus cytome assay (CBMN-cyt) in HepG2 cells. We also screened trimeroside into different human tumoral cell lines by sulforhodamine B (SRB) assay. Mutagenicity was detected in TA100 strain with metabolic activation. Genotoxic effects were not observed in HepG2 by comet assay. However, a decrease in the nuclear index division in the 2.0 mg·mL-1 concentration and an increase of nucleoplasmic bridges in the 1.5 mg·mL-1 concentration were detected by CBMN-cyt assay indicating cytotoxic and mutagenic effects. In SRB assay, trimeroside showed weak antiproliferative activity against the cell lines.

Asunto(s)

Baccharis/química , Ciclohexenos/toxicidad , Glicósidos/toxicidad , Animales , Ensayo Cometa , Ciclohexenos/química , Ciclohexenos/aislamiento & purificación , Daño del ADN , Glicósidos/química , Glicósidos/aislamiento & purificación , Células HT29 , Células Hep G2 , Humanos , Células KB , Ratones , Pruebas de Micronúcleos , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/toxicidad , Pruebas de Toxicidad

RESUMEN

An efficient and facile general method for the synthesis of conduritol C analogs, taking advantage of an enantioselective biocatalysis process of monosubstituted benzenes, is described. The absolute stereochemical patterns of the target molecules (−)-conduritol C, (−)-bromo-conduritol C, and (−)-methyl-conduritol C were achieved by means of chemoenzymatic methods. The stereochemistry present at the homochiral cyclohexadiene-cis-1,2-diols derived from the arene biotransformation and the enantioselective ring opening of a non-isolated vinylepoxide derivative permitted the absolute configuration of the carbon bearing the hydroxyl groups at the target molecules to be established. All three conduritols and two intermediates were crystallized, and their structures were confirmed by X-ray diffraction. The three conduritols and intermediates were isostructural. The versatility of our methodology is noteworthy to expand the preparation of conduritol C analogs starting from toluene dioxygenase (TDO) monosubstituted arene substrates.

Asunto(s)

Ciclohexanoles/síntesis química , Ciclohexenos/síntesis química , Biocatálisis , Biotransformación , Cristalografía por Rayos X , Ciclohexanoles/química , Ciclohexenos/química , Modelos Moleculares , Estructura Molecular , Estereoisomerismo

RESUMEN

Tooth decay is a major public health problem which affects a large number of people in several countries. Even though more than 700 bacterial species have been detected in the oral cavity, Streptococcus and Lactobacillus stand out as the genera that cause tooth decay and other periodontal diseases. In this study, essential oils from Citrus aurantifolia leaves (CL-EO) and fruit peel (CP-EO) were obtained by hydrodistillation by a Clevenger-type apparatus whereas their chemical composition was analyzed by gas chromatography-flame ionization detector (GC-FID) and gas chromatography-mass spectrometry (GC-MS). Limonene (77.5 %), linalool (20.1 %), citronellal (14.5 %) and citronellol (14.2 %) were the main constituents found in the essential oils from C. aurantifolia leaves and fruit peel. Antibacterial activity of essential oils was evaluated in terms of its minimum inhibitory concentration (MIC) values by the broth microdilution method in 96-well microplates. Both CL-EO and CP-EO displayed some activity against all oral pathogens under investigation; MIC values ranged from 20 to 200 µg/mL. CL-EO and CP-EO not only had promising activity against Streptococcus mutans (MIC = 20 µg/mL) and Lactobacillus casei (31.25 µg/mL), but also displayed antibacterial activity against all studied cariogenic bacteria. Efficacy of essential oils against S. mutans and L. casei is noteworthy and should be further investigated.

Asunto(s)

Antibacterianos , Citrus/química , Caries Dental/tratamiento farmacológico , Aceites Volátiles , Extractos Vegetales , Hojas de la Planta/química , Streptococcus/efectos de los fármacos , Monoterpenos Acíclicos , Aldehídos/química , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Ciclohexenos/química , Cromatografía de Gases y Espectrometría de Masas , Lacticaseibacillus casei/efectos de los fármacos , Limoneno , Pruebas de Sensibilidad Microbiana , Monoterpenos/química , Aceites Volátiles/química , Aceites Volátiles/aislamiento & purificación , Aceites Volátiles/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Terpenos/química

RESUMEN

The present study used isometric tension recording to investigate the vasorelaxant effect of limonene (LM), carveol (CV), and perillyl alcohol (POH) on contractility parameters of the rat aorta, focusing in particular on the structure-activity relationship. LM, CV, and POH showed a reversible inhibitory effect on the contraction induced by electromechanical and pharmacomechanical coupling. In the case of LM, but not CV and POH, this effect was influenced by preservation of the endothelium. POH and CV but not LM exhibited greater pharmacological potency on BayK-8644-induced contraction and on electromechanical coupling than on pharmacomechanical coupling. In endothelium-denuded preparations, the order of pharmacological potency on electrochemical coupling was LM < CV < POH. These compounds inhibited also, with grossly similar pharmacological potency, the contraction induced by phorbol ester dibutyrate. The present results suggest that LM, CV and POH induced relaxant effect on vascular smooth muscle by means of different mechanisms likely to include inhibition of PKC and IP3 pathway. For CV and POH, hydroxylated compounds, it was in electromechanical coupling that the greater pharmacological potency was observed, thus suggesting a relative specificity for a mechanism likely to be important in electromechanical coupling, for example, blockade of voltage-dependent calcium channel.

Asunto(s)

Ácido 3-piridinacarboxílico, 1,4-dihidro-2,6-dimetil-5-nitro-4-(2-(trifluorometil)fenil)-, Éster Metílico/metabolismo , Aorta Torácica/fisiología , Contracción Isométrica/efectos de los fármacos , Músculo Liso Vascular/fisiología , Vasodilatadores/farmacología , Animales , Aorta Torácica/efectos de los fármacos , Monoterpenos Ciclohexánicos , Ciclohexenos/química , Ciclohexenos/farmacología , Limoneno , Estructura Molecular , Monoterpenos/química , Monoterpenos/farmacología , Músculo Liso Vascular/efectos de los fármacos , Fenilefrina/efectos adversos , Forbol 12,13-Dibutirato/efectos adversos , Ratas , Relación Estructura-Actividad , Terpenos/química , Terpenos/farmacología , Vasodilatadores/química

RESUMEN

AIMS: This study evaluated parameters of toxicity and antiproliferative effects of (+)-N(1)-4-fluorobenzaldehyde-N(4)-{1-methyl-1-[(1R)-4-methylcyclohexene-3-il]-ethyl}-thiossemicarbazone (4-FTSC) in PC-3 adenocarcinoma prostate cells. MAIN METHODS: Cytotoxicity of 4-FTSC in PC-3 cells was evaluated using MTT assay. Morphology examination of PC-3 cells treated with 4-FTSC was also performed as well as the cell death mechanisms induced were investigated using flow cytometry. Parameters of toxicity of 4-FTSC was conducted by the investigation of its potential myelotoxicity and lymphotoxicity, hemolytic activity and acute oral toxicity profile. KEY FINDINGS: 4-FTSC showed promising cytotoxic effects against PC-3 cells (IC50 = 18.46 µM). It also triggered apoptotic morphological changes, phosphatidylserine externalization and a significant increase of DNA fragmentation in PC-3 cells. Moreover, 4-FTSC did not show changes in the PC-3 cell cycle with levels of p21, p27, NFĸB and cyclin D1 similar to those found in both control and treated cells. 4-FTSC also promoted an increase of p53 levels associated with mitochondrial impairment through loss of ∆Ψm and ROS overproduction. 4-FTSC-induced cell death mechanism in PC-3 cells involved activation of caspase-3/-7 through apoptosis intrinsic pathway via caspase-9. Regarding toxicological profile, 4-FTSC showed in vitro lymphotoxicity, although with low cytotoxicity for bone marrow progenitors and no hemolytic potential. Moreover, it was classified as GHS category 5 (LD50 > 2000-5000 mg/Kg), suggesting it has low acute oral systemic toxicity. SIGNIFICANCE: 4-FTSC seems to be a promising candidate to be used as a clinical tool in prostate cancer treatment. Further studies are required to better clarify its toxicopharmacological effects found in this compound.

Asunto(s)

Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Benzaldehídos/química , Ciclohexenos/farmacología , Neoplasias de la Próstata/patología , Tiosemicarbazonas/farmacología , Animales , Antineoplásicos/química , Células 3T3 BALB , Benzaldehídos/farmacología , Ciclo Celular , Proliferación Celular/efectos de los fármacos , Ciclohexenos/química , Humanos , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/metabolismo , Tiosemicarbazonas/química , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto

RESUMEN

Natural products obtained in dietary components may aid the prevention and treatment of a variety of diseases. Reports in the scientific literature have demonstrated that the consumption of terpenes is a successful alternative in the treatment of several diseases, triggering beneficial biological effects in clinical and preclinical studies. The monoterpene limonene is largely used in alimentary items, cleaning products, and it is one of the most frequent fragrances used in cosmetics formulation. The therapeutic effects of limonene have been extensively studied, proving anti-inflammatory, antioxidant, antinociceptive, anticancer, antidiabetic, antihyperalgesic, antiviral, and gastroprotective effects, among other beneficial effects in health. In this review, we collected, presented, and analyzed evidence from the scientific literature regarding the usage of limonene and its activities and underlying mechanisms involved in combating diseases. The highlighting of limonene applications could develop a useful targeting of innovative research in this field as well as the development of a limonene-based phytomedicine which could be used in a variety of conditions of health and disease.

Asunto(s)

Ciclohexenos/uso terapéutico , Síndrome Metabólico/prevención & control , Terpenos/uso terapéutico , Analgésicos/química , Analgésicos/farmacología , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/uso terapéutico , Antioxidantes/química , Antioxidantes/farmacología , Ciclohexenos/química , Ciclohexenos/farmacología , Humanos , Limoneno , Síndrome Metabólico/tratamiento farmacológico , Síndrome Metabólico/patología , Osteoartritis/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Plantas/química , Plantas/metabolismo , Terpenos/química , Terpenos/farmacología

RESUMEN

The objective of this study was to evaluate the antioxidant activity of rosemary essential oil fractions obtained by molecular distillation (MD) and investigate their effect on the oxidative stability of sunflower oil. MD fractions were prepared in a series of low-pressure stages where rosemary essential oil was the first feed. Subsequently, a distillate (D1) and residue (R1) were obtained and the residue fraction from the previous stage used as the feed for the next. The residue fractions had the largest capacity to capture free radicals, and the lowest peroxide values, conjugated dienes and conjugated trienes. The antioxidant activity of the fractions was due to oxygenated monoterpenes, specifically α-terpineol and cis-sabinene hydrate. Oxidative stability results showed the residues (R1 and R4) and butylated hydroxytoluene had greater antioxidant activity than either the distillate fractions or original rosemary essential oil. The residue fractions obtained by short path MD of rosemary essential oil could be used as a natural antioxidants by the food industry.

Asunto(s)

Antioxidantes/farmacología , Hidroxitolueno Butilado/farmacología , Conservación de Alimentos/métodos , Aceites Volátiles/farmacología , Aceite de Girasol/química , Antioxidantes/química , Monoterpenos Bicíclicos , Hidroxitolueno Butilado/aislamiento & purificación , Monoterpenos Ciclohexánicos , Ciclohexenos/química , Ciclohexenos/aislamiento & purificación , Ciclohexenos/farmacología , Destilación , Radicales Libres/química , Monoterpenos/química , Monoterpenos/aislamiento & purificación , Monoterpenos/farmacología , Aceites Volátiles/química , Oxidación-Reducción/efectos de los fármacos

RESUMEN

Baccharis reticularia DC. is a plant species from the Asteraceae family that is endemic to Brazil. Despite the great importance of Baccharis genus, no study has been carried out regarding either the phytochemical composition of B. reticularia or the evaluation of its larvicidal potential. Considering the intrinsic immiscibility of essential oils, this study shows larvicidal nanoemulsions containing the B. reticularia phytochemically characterized essential oil and its main constituent against Aedes aegypti. The major compound found was d-limonene (25.7%). The essential oil inhibited the acetylcholinesterase, one of the main targets of insecticides. The required hydrophile-lipophile balance of both nanoemulsions was 15.0. The mean droplet sizes were around 90.0 nm, and no major alterations were observed after 24 h of preparation for both formulations. After 48 h of treatment, the estimated LC50 values were 118.94 µg mL-1 and 81.19 µg mL-1 for B. reticularia essential oil and d-limonene nanoemulsions, respectively. Morphological alterations evidenced by scanning electron micrography were observed on the larvae treated with the d-limonene nanoemulsion. This paper demonstrated a simple and ecofriendly method for obtaining B. reticularia essential oil and d-limonene aqueous nanoemulsions by a non-heating and solvent-free method, as promising alternatives for Aedes aegypti control.

Asunto(s)

Baccharis/química , Ciclohexenos/química , Ciclohexenos/farmacología , Insecticidas/química , Insecticidas/farmacología , Terpenos/química , Terpenos/farmacología , Aedes/efectos de los fármacos , Animales , Brasil , Cromatografía de Gases y Espectrometría de Masas , Larva/efectos de los fármacos , Limoneno , Control de Mosquitos , Aceites Volátiles/química , Aceites Volátiles/farmacología , Fitoquímicos/química , Fitoquímicos/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología

RESUMEN

Edible films (EFs) have gained great interest due to their ability to keep foods safe, maintaining their physical and organoleptic properties for a longer time. The aim of this work was to develop EFs based on a chitosan-zein mixture with three different essential oils (EOs) added: anise, orange, and cinnamon, and to characterize them to establish the relationship between their structural and physical properties. The addition of an EO into an EF significantly affected (p < 0.05) the a* (redness/greenness) and b* (yellowness/blueness) values of the film surface. The EFs presented a refractive index between 1.35 and 1.55, and thus are classified as transparent. The physical properties of EFs with an added EO were improved, and films that incorporated the anise EO showed significantly lower water vapor permeability (1.2 ± 0.1 g mm h-1 m-2 kPa-1) and high hardness (104.3 ± 3.22 MPa). EFs with an added EO were able to inhibit the growth of Penicillium sp. and Rhizopus sp. to a larger extent than without an EO. Films' structural changes were the result of chemical interactions among amino acid side chains from zein, glucosamine from chitosan, and cinnamaldehyde, anethole, or limonene from the EOs as detected by a Raman analysis. The incorporation of an EO in the EFs' formulation could represent an alternative use as coatings to enhance the shelf life of food products.

Asunto(s)

Antifúngicos/química , Quitosano/química , Embalaje de Alimentos , Aceites Volátiles/química , Zeína/química , Acroleína/análogos & derivados , Acroleína/química , Derivados de Alilbenceno , Anisoles/química , Ciclohexenos/química , Limoneno , Penicillium/efectos de los fármacos , Polímeros/farmacología , Refractometría , Rhizopus/efectos de los fármacos , Propiedades de Superficie , Terpenos/química

RESUMEN

The Protium heptaphyllum species, also known as Almécega, produces an oily resin, used in folk medicine as an analgesic and anti-inflammatory agent, in healing, and as an expectorant, which is rich in pentacyclic triterpenes and essential oils. In this study, the essential oil obtained by hydrodistillation of Almécega's resin was analyzed by gas chromatography-triple quadrupole mass spectrometry and evaluated for chemical composition and vasorelaxant activity in rat superior mesenteric artery. The main constituents determined by gas chromatography-triple quadrupole mass spectrometry were limonene, p-cineole, and o-cymene. In intact rings precontracted with phenylephrine (Phe 1 µM), EOPh (3-750 µg/mL) induced relaxation, and the essential oil had a concentration-dependent vasorelaxant effect, without involvement of endothelial mediators.

Asunto(s)

Burseraceae/química , Aceites Volátiles/química , Analgésicos/química , Analgésicos/farmacología , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Ciclohexenos/química , Ciclohexenos/farmacología , Células Endoteliales/efectos de los fármacos , Cromatografía de Gases y Espectrometría de Masas/métodos , Limoneno , Masculino , Aceites Volátiles/farmacología , Fenilefrina/química , Fenilefrina/farmacología , Ratas , Ratas Wistar , Resinas de Plantas/química , Terpenos/química , Terpenos/farmacología , Vasodilatadores/química , Vasodilatadores/farmacología

RESUMEN

The aim of this work was to study the use of different prebiotic biopolymers in lime essential oil microencapsulation. Whey protein isolate, inulin and oligofructose biopolymers were used. The addition of prebiotic biopolymers reduced emulsion viscosity, although it produced larger droplet sizes (0.31-0.32 µm). Moisture values (2.94-3.13 g/100 g dry solids) and water activity (0.152-0.185) were satisfactory, being within the appropriate range for powdered food quality. Total oil content, limonene retention values and antioxidant activity of the microparticles containing essential oil decreased in the presence of the carbohydrates. The addition of prebiotic biopolymers reduced the microparticle thermal stability. X-ray diffraction confirmed the amorphous characteristic of the microparticles and the interaction of the essential oil with the wall material. The presence of prebiotic biopolymers can be a good alternative for lime essential oil microparticles, mainly using fibre that has a functional food appeal and can improve consumer health.

Asunto(s)

Compuestos de Calcio/química , Inulina/química , Aceites Volátiles/química , Oligosacáridos/química , Óxidos/química , Biopolímeros/química , Ciclohexenos/química , Emulsiones , Limoneno , Tamaño de la Partícula , Prebióticos , Terpenos/química , Viscosidad

RESUMEN

This study evaluated three different methods for the formation of an inclusion complex between alpha- and beta-cyclodextrin (α- and ß-CD) and limonene (LIM) with the goal of improving the physicochemical properties of limonene. The study samples were prepared through physical mixing (PM), paste complexation (PC), and slurry complexation (SC) methods in the molar ratio of 1:1 (cyclodextrin:limonene). The complexes prepared were evaluated with thermogravimetry/derivate thermogravimetry, infrared spectroscopy, X-ray diffraction, complexation efficiency through gas chromatography/mass spectrometry analyses, molecular modeling, and nuclear magnetic resonance. The results showed that the physical mixing procedure did not produce complexation, but the paste and slurry methods produced inclusion complexes, which demonstrated interactions outside of the cavity of the CDs. However, the paste obtained with ß-cyclodextrin did not demonstrate complexation in the gas chromatographic technique because, after extraction, most of the limonene was either surface-adsorbed by ß-cyclodextrin or volatilized during the procedure. We conclude that paste complexation and slurry complexation are effective and economic methods to improve the physicochemical character of limonene and could have important applications in pharmacological activities in terms of an increase in solubility.

Asunto(s)

Ciclohexenos/química , Terpenos/química , alfa-Ciclodextrinas/química , beta-Ciclodextrinas/química , Cromatografía de Gases/métodos , Limoneno , Espectroscopía de Resonancia Magnética/métodos , Espectrometría de Masas/métodos , Modelos Moleculares , Solubilidad , Espectrofotometría Infrarroja/métodos , Termogravimetría/métodos , Difracción de Rayos X/métodos

RESUMEN

This work evaluated the in vitro and in vivo activity of TDZ 2 on Trypanosoma cruzi amastigotes and determined the possible mechanism of action of this compound on T. cruzi death. TDZ 2 inhibited T. cruzi proliferation in vitro and had low haemolytic potential. It also induced morphological and ultrastructural alterations. We observed a reduction of cell volume, the depolarization of the mitochondrial membrane, an increase in ROS production, lipoperoxidation of the cell membrane, lipid bodies formation and production of nitric oxide, a decrease in reduced thiols levels and, presence of autophagic vacuoles. The in vivo study found a reduction of parasitemia in animals treated with TDZ 2 alone or combined with benznidazole. Altogether, the alterations induced by TDZ 2 point to an oxidative stress condition that lead to T. cruzi cell death.

Asunto(s)

Antiprotozoarios/farmacología , Benzaldehídos/farmacología , Ciclohexenos/farmacología , Estrés Oxidativo , Terpenos/farmacología , Tiadiazoles/farmacología , Tiosemicarbazonas/farmacología , Trypanosoma cruzi/efectos de los fármacos , Animales , Antiprotozoarios/química , Benzaldehídos/química , Enfermedad de Chagas/tratamiento farmacológico , Enfermedad de Chagas/parasitología , Ciclohexenos/química , Modelos Animales de Enfermedad , Femenino , Humanos , Limoneno , Ratones Endogámicos BALB C , Estructura Molecular , Carga de Parásitos , Parasitemia/tratamiento farmacológico , Parasitemia/parasitología , Terpenos/química , Tiadiazoles/química , Tiosemicarbazonas/química , Resultado del Tratamiento , Trypanosoma cruzi/crecimiento & desarrollo , Trypanosoma cruzi/fisiología , Trypanosoma cruzi/ultraestructura

RESUMEN

One of the main goals of chemistry is to understand the underlying principles of chemical reactions, in terms of both its reaction mechanism and the thermodynamics that govern it. Using hybrid quantum mechanics/molecular mechanics (QM/MM)-based methods in combination with a biased sampling scheme, it is possible to simulate chemical reactions occurring inside complex environments such as an enzyme, or aqueous solution, and determining the corresponding free energy profile, which provides direct comparison with experimental determined kinetic and equilibrium parameters. Among the most promising biasing schemes is the multiple steered molecular dynamics method, which in combination with Jarzynski's Relationship (JR) allows obtaining the equilibrium free energy profile, from a finite set of nonequilibrium reactive trajectories by exponentially averaging the individual work profiles. However, obtaining statistically converged and accurate profiles is far from easy and may result in increased computational cost if the selected steering speed and number of trajectories are inappropriately chosen. In this small review, using the extensively studied chorismate to prephenate conversion reaction, we first present a systematic study of how key parameters such as pulling speed, number of trajectories, and reaction progress are related to the resulting work distributions and in turn the accuracy of the free energy obtained with JR. Second, and in the context of QM/MM strategies, we introduce the Hybrid Differential Relaxation Algorithm, and show how it allows obtaining more accurate free energy profiles using faster pulling speeds and smaller number of trajectories and thus smaller computational cost.

Asunto(s)

Amidohidrolasas/química , Proteínas Bacterianas/química , Corismato Mutasa/química , Ácido Corísmico/química , Ácidos Ciclohexanocarboxílicos/química , Ciclohexenos/química , Algoritmos , Amidohidrolasas/metabolismo , Bacillus subtilis/química , Bacillus subtilis/enzimología , Proteínas Bacterianas/metabolismo , Corismato Mutasa/metabolismo , Ácido Corísmico/metabolismo , Ácidos Ciclohexanocarboxílicos/metabolismo , Ciclohexenos/metabolismo , Cinética , Simulación de Dinámica Molecular , Mycobacterium tuberculosis/química , Mycobacterium tuberculosis/enzimología , Teoría Cuántica , Electricidad Estática , Especificidad por Sustrato , Termodinámica

RESUMEN

The lesser mealworm, Alphitobius diaperinus Panzer 1797 (Coleoptera: Tenebrionidae), is a cosmopolitan insect pest affecting poultry production. Due to its cryptic behavior, insecticide control is usually not efficient. Thus, sustainable and effective methods would have an enormous and positive impact in poultry production. The aim of this study was to confirm the identity of the male-produced aggregation pheromone for a Brazilian population of A. diaperinus and to evaluate its biological activity in behavioral assays. Six male-specific compounds were identified: (R)-limonene (1), (E)-ocimene (2), 2-nonanone (3), (S)-linalool (4), (R)-daucene (5), all described before in an American population, and a sixth component, (E,E)-α-farnesene (6), which is apparently exclusive to a Brazilian population. Y-Tube bioassays confirmed the presence of a male-produced aggregation pheromone and showed that all components need to be present in a similar ratio and concentration as emitted by male A. diaperinus to produce a positive chemotactic response.

Asunto(s)

Quimiotaxis , Feromonas/química , Tenebrio/efectos de los fármacos , Monoterpenos Acíclicos , Alquenos/química , Animales , Conducta Animal , Brasil , Compuestos Bicíclicos con Puentes/química , Cromatografía de Gases , Ciclohexenos/química , Femenino , Cromatografía de Gases y Espectrometría de Masas , Cetonas/química , Limoneno , Masculino , Monoterpenos/química , Olfatometría , Sesquiterpenos/química , Terpenos/química , Compuestos Orgánicos Volátiles/química

RESUMEN

The effect of an extra EWG in the reactivity and regioselectivity in Diels-Alder reactions of ß-cyanolevoglucosenone and 4 different dienes was studied by a joint computational and experimental study. Conceptual DFT analysis successfully predicted an important enhancement in the reactivity, and correctly anticipated the regioselectivity in the reactions with isoprene. However, this static treatment failed when dealing the regiochemical preference of the reactions involving a substituted anthracene as diene. MPW1K/6-31G* calculations correctly reproduced the experimental observations. Based on the collected data, we found that when dealing with dienes and dienophiles with no clear electronically activated position, the ease of pyramidalization of the interacting atoms dictates the regioselectivity of the DA reaction.

Asunto(s)

Alquenos/química , Butanos/química , Carbohidratos/química , Biología Computacional , Reacción de Cicloadición , Ciclohexenos/química , Antracenos/química , Butadienos/química , Ciclopentanos/química , Hemiterpenos/química , Cetonas/química , Pentanos/química , Estereoisomerismo

RESUMEN

Laureliopsis philippiana (Looser) R. Schodde (Monimiaceae) is a native tree widespread in the forest areas in the south of Chile and Argentina, known for its medicinal properties and excellent wood. The aim of this study was to evaluate the chemical composition of L. philippiana leaf and bark essential oils (EOs) using gas chromatography-mass spectrometry (GC-MS), and to quantify its anti-oomycete activity, specifically against Saprolegnia parasitica and S. australis. Only six components were identified in leaf EO, 96.92% of which are phenylpropanoids and 3.08% are terpenes. As for bark EO, 29 components were identified, representing 67.61% for phenylpropanoids and 32.39% for terpenes. Leaf EO was characterized mainly by safrole (96.92%) and ß-phellandrene (1.80%). Bark EO was characterized mainly by isosafrole (30.07%), safrole (24.41%), eucalyptol (13.89%), methyleugenol (7.12%), and eugenol (6.01%). Bark EO has the most promising anti-Saprolegnia activity, with a minimum inhibition concentration (MIC) value of 30.0 µg/mL against mycelia growth and a minimum fungicidal concentration (MFC) value of 50.0 µg/mL against spores; for leaf EO, the MIC and MFC values are 100 and 125 µg/mL, respectively. These findings demonstrate that bark EO has potential to be developed as a remedy for the control of Saprolegnia spp. in aquaculture.

Asunto(s)

Antifúngicos/química , Antifúngicos/farmacología , Aceites Volátiles/química , Aceites Volátiles/farmacología , Oomicetos/efectos de los fármacos , Saprolegnia/efectos de los fármacos , Argentina , Chile , Monoterpenos Ciclohexánicos , Ciclohexenos/química , Ciclohexenos/farmacología , Pruebas de Sensibilidad Microbiana , Monoterpenos/química , Monoterpenos/farmacología , Micelio/efectos de los fármacos , Corteza de la Planta/química , Hojas de la Planta/química , Aceites de Plantas/química , Aceites de Plantas/farmacología , Terpenos/química , Terpenos/farmacología

RESUMEN

The goal of the present study was to evaluate the acaricidal potential of Lippia alba essential oil, citral chemotypes (LA-10 and LA-44 genotypes) and carvone chemotypes (LA-13 and LA-57 genotypes), as well as purified citral and enantiomers of carvone and limonene. Efficacy against Rhipicephalus microplus was assessed by the larval packet and the engorged female immersion tests. Citral chemotypes had greater larvicidal activity than carvone chemotypes, and this was further supported by larvicidal and adulticidal activity of purified citral with LC50 values of 7.0 and 29.8 mg/mL, respectively. While purified enantiomers of carvone exhibited greater larvicidal activity than those of limonene, enantioselectivity of limonene was observed with R-(+) displaying significantly higher efficacy (LC50 of 31.2mg/mL) than S-(-) (LC50 of 54.5mg/mL). The essential oils and purified compounds were much less toxic toward engorged adult females, with the exception of citral, and this may be due to limited cuticular penetration.

Asunto(s)

Acaricidas/farmacología , Genotipo , Lippia/química , Aceites Volátiles/farmacología , Aceites de Plantas/farmacología , Rhipicephalus/efectos de los fármacos , Acaricidas/química , Monoterpenos Acíclicos , Animales , Monoterpenos Ciclohexánicos , Ciclohexenos/química , Ciclohexenos/farmacología , Femenino , Limoneno , Lippia/genética , Monoterpenos/química , Monoterpenos/farmacología , Aceites Volátiles/química , Aceites de Plantas/química , Terpenos/química , Terpenos/farmacología