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The leaves of Nectandra laurel Klotzsch ex Nees, belonging to the family, Lauraceae, were collected in the province of Loja (Ecuador), dried, and analytically steam-distilled. An unprecedented essential oil was obtained, with a 0.03% yield by weight of dry plant material. The volatile fraction was submitted to qualitative (GC-MS) and quantitative (GC-FID) chemical analysis, on two orthogonal stationary phases. Seventy-eight compounds were detected and quantified on at least one column. The essential oil was dominated by sesquiterpene hydrocarbons (53.0-53.8% on the non-polar and polar stationary phase, respectively), followed by oxygenated sesquiterpenoids (18.9-19.0%). A third group was constituted by metabolites of other origins, mainly aliphatic compounds, apparently derived from the acetate pathway (11.7-8.5%). The major components of the EO (≥3.0% with at least one column) were δ-selinene (30.5-28.8%), δ-cadinene (5.4-6.4%), epi-α-cadinol (4.9-5.2%), an undetermined compound with a molecular weight of 204 (3.4-4.2%), α-pinene (3.3-2.9%), and α-cadinol (2.9-3.0%). Finally, the essential oil was submitted to enantioselective analysis, on two ß-cyclodextrin-based chiral selectors, determining the enantiomeric distribution of seven chiral terpenes. Among them, (1R,5R)-(+)-α-pinene, (1R,5R)-(+)-ß-pinene, and (R)-(-)-α-phellandrene were enantiomerically pure, whereas camphene, borneol, α-copaene, and α-terpineol were present as scalemic mixtures.

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The fresh leaves of Gynoxys laurifolia (Kunth) Cass. (Asteraceae), collected in the province of Loja (Ecuador), were submitted to steam distillation, producing an essential oil with a yield of 0.02% by weight. This volatile fraction, described here for the first time, was submitted to qualitative (GC-MS) and quantitative (GC-FID) chemical analyses, on two orthogonal columns (non-polar and polar stationary phase). A total of 90 components, corresponding to 95.9-95.0% by weight on the non-polar and polar stationary phase, respectively, were detected and quantified with at least one column. Major constituents (≥3%) were: germacrene D (18.9-18.0%), (E)-ß-caryophyllene (13.2-15.0%), α-pinene (11.0-10.3%), ß-pinene (4.5-4.4%), ß-phellandrene (4.0-3.0%), bicyclogermacrene (4.0-3.0%), and bakkenolide A (3.2-3.4%). This essential oil was dominated by sesquiterpene hydrocarbons (about 45%), followed by monoterpene hydrocarbons (about 25-30%). This research was complemented with the enantioselective analysis of some common chiral terpenes, carried out through 2,3-diethyl-6-tert-butyldimethylsilyl-ß-cyclodextrin and 2,3-diacetyl-6-tert-butyldimethylsilyl-ß-cyclodextrin as stationary phase chiral selectors. As a result, (1S,5S)-(-)-ß-pinene, (R)-(-)-α-phellandrene, (R)-(-)-ß-phellandrene, (S)-(-)-limonene, (S)-(+)-linalyl acetate, and (S)-(-)-germacrene D were observed as enantiomerically pure compounds, whereas α-pinene, linalool, terpinene-4-ol, and α-terpineol were present as scalemic mixtures. Finally, sabinene was practically racemic. Due to plant wildness and the relatively low distillation yield, no industrial applications can be identified, in the first instance for this essential oil. The focus of the present study is therefore academic.

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An essential oil, distilled from the leaves of the Andean species Gynoxys rugulosa Muschl., is described in the present study for the first time. The chemical composition was qualitatively and quantitatively determined by GC-MS and GC-FID, respectively. On the one hand, the qualitative composition was obtained by comparing the mass spectrum and the linear retention index of each component with data from literature. On the other hand, the quantitative composition was determined by calculating the relative response factor of each constituent, according to its combustion enthalpy. Both analyses were carried out with two orthogonal columns of nonpolar and polar stationary phases. A total of 112 compounds were detected and quantified with at least one column, corresponding to 87.3-93.0% of the whole oil mass. Among the 112 detected components, 103 were identified. The main constituents were α-pinene (5.3-6.0%), (E)-ß-caryophyllene (2.4-2.8%), α-humulene (3.0-3.2%), germacrene D (4.9-6.5%), δ-cadinene (2.2-2.3%), caryophyllene oxide (1.6-2.2%), α-cadinol (3.8-4.4%), 1-nonadecanol (1.7-1.9%), 1-eicosanol (0.9-1.2%), n-tricosane (3.3-3.4%), 1-heneicosanol (4.5-5.8%), n-pentacosane (5.8-7.1%), 1-tricosanol (4.0-4.5%), and n-heptacosane (3.0-3.5%). Furthermore, an enantioselective analysis was carried out on the essential oil, by means of two cyclodextrin-based capillary columns. The enantiomers of α-pinene, ß-pinene, sabinene, α-phellandrene, ß-phellandrene, linalool, α-copaene, terpinen-4-ol, α-terpineol, and germacrene D were detected, and the respective enantiomeric excess was calculated.

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BACKGROUND: The amino acids R- and S-proline were used to synthesize novel neonicotinoid derivatives that, after being characterized by 1 H, DEPTQ 135, and HRMS-QTOF, were evaluated for use as insecticides against Galleria mellonella (caterpillar), Sitophilus zeamais, Xylosandrus morigerus, Xyleborus affinis, and Xyleborus ferrugineus. RESULTS: Comparisons of biological activity and absolute configuration showed that the R enantiomer had excellent and outstanding insecticidal activity against the insects tested, with up to 100% mortality after 12 h compared with dinotefuran at the same concentration. CONCLUSIONS: The results suggest that compound R6 is an excellent lead enantiopure insecticide for future development in the field of crop protection. Furthermore, intermolecular interactions between nicotinic acetylcholine receptors and the R enantiomer displays a lower score which mean a higher affinity to the nAChR receptor and the π-π interactions are more stable than the S derivative. © 2023 Society of Chemical Industry.

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SUMMARY Introduction: Cannabidiol (CBD) has become a promising bioactive for the next decades after the recent recognition of the medical potential of Cannabis derivatives by United Nations member countries, as it has no psychotropic potential as your isomer A9-tetrahydrocannabinol (Δ9-THC). The differentiation of these isomers has been studied for decades. Recent studies demonstrate that even with more subtle chemical characteristics, such as those of the CBD enantiomers, there are considerable bioactive differences. However, there are still not many studies on their chemical structures. Aim: This work aims to present experimental data obtained by Nuclear Magnetic Resonance (NMR) to better elucidate the three-dimensional structure of this enantiomeric bioactive. Materials and methods: For this, a sample of non-synthetic high purity CBD was subjected to different one-dimensional (1D-NMR) and two-dimensional (2D-NMR) analyses related to the hydrogen (1H) and carbon (13C) nuclei. Results and discussion: The 1D-NMR techniques used are sufficient to distinguish the CBD and Δ 9-THC isomers, but not to identify the enantiomeric characteristics of the non-synthetic CBD. Conclusions: It is concluded that the two-dimensional homonuclear (1H,1H) and heteronuclear (1H,13C) techniques analyzed are suitable to help distinguish CBD enantiomers.

Introducción: El cannabidiol (CBD) se ha convertido en un bioactivo prometedor para las próximas décadas tras el reciente reconocimiento del potencial medicinal de los derivados del Cannabis por parte de los países miembros de las Naciones Unidas, ya que no tiene potencial psicotrópico como su isómero Δ9-tetrahidrocannabinol (Δ 9-THC). La diferenciación de estos isómeros se ha estudiado durante décadas. Estudios recientes demuestran que incluso con características químicas más sutiles, como las de los enan-tiómeros del CBD, existen diferencias bioactivas considerables. Sin embargo, no existen muchos estudios sobre sus estructuras químicas. Objetivo: Este trabajo tiene como objetivo presentar datos experimentales obtenidos por Resonancia magnética nuclear (RMN) para dilucidar mejor la estructura tridimensional de este bioactivo enantiomérico. Materiales y métodos: Para ello, una muestra de CBD no sintético de alta pureza se sometió a diferentes análisis unidimensionales (RMN-1D) y bidimensionales (RMN-2D) relacionados con los núcleos del hidrógeno (1H) y carbono (13C). Resultados y discusión: Las técnicas de RMN-1D utilizadas son suficientes para distinguir los isómeros de CBD y Δ 9-THC, pero no para identificar las características enantioméricas del CBD no sintético. Conclusiones: Se concluye que las técnicas bidimensionales homonucleares (1H,1H) y heteronucleares (1H,13C) analizadas son adecuadas para ayudar a distinguir los enantiómeros del CBD.

Introdução: O canabidiol (CBD) se tornou um bioativo promissor para as próximas décadas após o recente reconhecimento do potencial medicinal dos derivados da Cannabis pelos países membros das Nações Unidas, uma vez que não tem potencial psicotrópico como seu isômero Δ 9-tetrahidrocanabinol (A9-THC). A diferenciação desses isômeros é estudada há décadas. Estudos recentes demonstram que mesmo com características químicas mais sutis, como as dos enantiômeros do CBD, há consideráveis diferenças bioativas. Todavia, ainda não há muitos estudos sobre suas estruturas químicas. Objetivo: Este trabalho tem como objetivo apresentar dados experimentais obtidos por Ressonância magnética nuclear (RMN) para melhor elucidar a estrutura tridimensional deste bioativo enantiomérico. Materiais e métodos: Para isso, uma amostra de CBD não sintético de alta pureza foi submetida a diferentes análises unidimensionais (RMN-1D) e bidimensionais (RMN-2D) relacionadas aos núcleos de hidrogênio (1H) e carbono (13C). Resultados e discussão: As técnicas de RMN-1D usadas são suficientes para distinguir os isômeros CBD e Δ 9-THC, mas não para identificar as características enantioméricas do CBD não sintético. Conclusões: Conclui-se que as técnicas bidimensionais homonucleares (1H,1H) e heteronucleares (1H,13C) analisadas são adequadas para auxiliar na distinção dos enantiômeros do CBD.

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Carvedilol is a commonly used antihypertensive whose oral absorption is limited by low solubility and significant first-pass metabolism. This work aimed to apply chemometrics for the optimization of a salting-out assisted liquid-liquid extraction (SALLE) combined with LC-MS/MS to analyze carvedilol enantiomers in plasma samples. Method development and validation were driven for application in pharmacokinetic studies. Parameters that influence the efficiency of SALLE were evaluated using a fractional factorial 24-1 design with 4 factors and a central composite design was used to evaluate the optimal extraction condition. Carvedilol enantiomers and the internal standard lidocaine were separated on an Astec® Chirobiotic® V column and a mixture of methanol:ethanol (90:10, v/v) with 0.02% diethylamine and 0.18% acetic acid as mobile phase. The positive ion mode on electrospray ionization was used to monitor the transitions of m/z 407 > 100 and 235 > 86 for carvedilol enantiomers and lidocaine, respectively. Acetonitrile and ammonium acetate solution were selected for sample preparation by SALLE. Surface graphs and the desirability test were used to define the optimized SALLE conditions which resulted in 93% recovery for both carvedilol enantiomers. The method was linear in the range of 0.5 to 100 ng/mL in plasma, with a lower limit of quantification of 0.5 ng/mL. Within-run and between-run precision (as the relative standard deviation) were all < 9.74% and accuracy (as relative error) did not exceed ± 10.30%. Residual effect and matrix effect were not observed. Carvedilol enantiomers were stable in plasma under the storage, preparation, and analysis conditions. The validated method was successfully applied to analyze carvedilol in plasma samples from patients previously submitted to a Roux-en-Y gastric bypass surgery treated with a single oral dose of 25 mg racemic-carvedilol. Higher plasma concentrations were observed for (R)-(+)-carvedilol when compared to (S)-(-)-carvedilol in two patients post-bariatric surgery.

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The aim of this study was to extract and identify the chemical compounds of Diplosthephium juniperinum essential oil (EO) from Ecuador and to assess its anticholinesterase and antioxidant properties. The EO chemical composition was determined by GC−MS. A total of 74 constituents of EO were identified, representing 97.27% in DB-5ms and 96.06% in HP-INNOWax of the total EO. The major constituents (>4.50%) identified were: α-pinene (21.52, 22.04%), geranyl acetate (10.54, 7.78%), silphiper-fol-5-ene (8.67, 7.38%), α-copaene (8.26, 8.18%), 7-epi-silphiperfol-5-ene (4.93, 5.95%), and germacrene D (4.91, 6.00%). Enantioselective analysis of the volatile fraction of D. juniperinum showed: (+)-α-pinene as a pure enantiomer and 5 pairs of enantiomeric compounds. Among them, (−)-ß-Pinene and (−)-Germacrene D presented a high enantiomeric excess of 93.23 and 84.62%, respectively, while (−)-α-Thujene, (−)-Sabinene and (S)-4-Terpineol with a lower enantiomeric excess of 56.34, 47.84 and 43.11%, respectively. A moderate inhibitory effect was observed for Acetylcholinesterase (AChE) and Butyrylcholinesterase (BuChE) enzymes with IC50 values of 67.20 ± 7.10 and 89.00 ± 9.90 µg/mL, respectively. A lower antioxidant potential was observed for the EO measured through DPPH and ABTS radical scavenging assays with SC50 values of 127.03 and >1000 µg/mL, respectively. To the best of our knowledge, this is the first report of the chemical composition, enantiomeric distribution and, anticholinesterase and antioxidant potential of the EO of D. juniperinum. As future perspective, further in-vivo studies could be conducted to confirm the anticholinesterase potential of the EO.

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Limonene-1,2-diol is a limonene oxygenated metabolite that possesses eight different stereoisomers, which could result in different biological properties. Nonetheless, the relation between its spatial configuration and biological function is still little explored. The present study aimed to perform the stereoisomers identification using nuclear magnetic resonance (NMR) investigation of the limonene-1,2-diol produced via R-(+)- and S-(-)-limonene biotransformation by Colletotrichum nymphaeae and S-(-)-limonene biotransformation by Fusarium oxysporum 152B. Besides, in vitro antiproliferative activity was evaluated against human tumor and nontumor cell lines. The NMR analysis showed that R-(+)-limonene biotransformation afforded exclusively (+)-(1S,2S,4R-limonene-1,2-diol), whereas S-(-)-limonene biotransformation afforded exclusively (-)-(1R,2R,4S-limonene-1,2-diol) independent on the fungi used. Despite no significant cytostatic effects, a possible influence of stereogenic center on the antiproliferative activity of these limonene biotransformation products was evidenced. Moreover, the lack of in vitro antiproliferative effect of limonene-1,2-diol against nontumor cells suggested a safe dose range for further in vivo evaluations, including food applications.

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Approximately one-third of individuals with major depressive disorder are resistant to conventional antidepressants (i.e., monoamine-based therapies), and, even among respondents, a proper therapeutic effect may require weeks of treatment. Ketamine, a racemic mixture of the two enantiomers, (R)-ketamine and (S)-ketamine, is an N-methyl-d-aspartate receptor (NMDAR) antagonist and has been shown to have rapid-acting antidepressant properties in patients with treatment-resistant depression (TRD). Although (R)-ketamine has a lower affinity for NMDAR, it presents greater potency and longer-lasting antidepressant properties, with no major side effects, than racemic ketamine or (S)-ketamine in preclinical findings. Thereby, ketamine and its enantiomers have not only an antagonistic effect on NMDAR but also a strong synaptogenic-modulatory effect, which is impaired in TRD pathophysiology. In this review, we summarize the current evidence regarding the modulation of neurotransmission, neuroplasticity, and neural network activity as putative mechanisms of these rapid-acting antidepressants, highlighting differences on intracellular signaling pathways of synaptic proteins such as mammalian target of rapamycin (mTOR), extracellular signal-regulated kinase (ERK) and brain-derived neurotrophic factor (BDNF). In addition, we discuss probable mechanisms involved in the side effects of ketamine and its enantiomers.

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Two methods using LC-MS/MS were validated to quantify citalopram (CTP) racemate [(R/S)-CTP] and the enantiomers (R)-CTP and (S)-CTP in human plasma, respectively. Paroxetine hydrochloride was used as the internal standard, and samples were extracted by protein precipitation with acetonitrile. The non-enantioselective method was conducted using a C18 column, and the mobile phase consisted of water for solvent A and acetonitrile for solvent B, both with 0.1% formic acid. For the chiral method, an analytical column Lux Cellulose-1 was used. Mobile phase A was composed of water with 0.025% of formic acid and 0.05% of diethylamine, and mobile phase B consisted of acetonitrile:2-propanol (95:5, v/v). No significant matrix effects were observed at the retention times of analytes and internal standard. The mean recovery was 89%, and the assays were linear in the concentration range of 1-50 and 5-30 ng/mL for the non-enantioselective and enantioselective methods, respectively. The intra- and inter-day precisions of both methods were less than 12.30%, and the accuracies were less than 12.13%. The validated methods were successfully applied to a pharmacokinetic study in which 20-mg CTP tablets were administered to healthy volunteers, and their plasma levels were monitored over time in a bioequivalence study. HIGHLIGHTS: Simple and rapid LC-MS/MS method for the quantification of citalopram and its enantiomers in human plasma. Both methods were demonstrated to be selective, reliable, and sensitive. Both methods have sufficient sensitivity to quantify the steady state through concentrations already reported for citalopram and escitalopram. Validated method presented in this study can be suitably applied to pharmacokinetic studies involving citalopram and escitalopram. Bland-Altman analysis suggested that non-enantioselective and enantioselective methods can be applied in pharmacokinetic studies.

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