RESUMO
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 %), ß-bisabolene (9.4 %), γ-elemene (7.6 %), (Z)- ß-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.
Assuntos
Amicacina , Antibacterianos , Farmacorresistência Bacteriana Múltipla , Sinergismo Farmacológico , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana , Óleos Voláteis , Amicacina/farmacologia , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Animais , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Antibacterianos/farmacologia , Klebsiella pneumoniae/efeitos dos fármacos , Cromatografia Gasosa-Espectrometria de Massas , Caenorhabditis elegans/efeitos dos fármacos , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Sesquiterpenos Monocíclicos/farmacologia , Sesquiterpenos Policíclicos/farmacologia , Sesquiterpenos Policíclicos/química , Sesquiterpenos/farmacologiaRESUMO
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.
Assuntos
Anti-Infecciosos , Drimys , Testes de Sensibilidade Microbiana , Sesquiterpenos , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Drimys/química , Sesquiterpenos Policíclicos/farmacologia , Sesquiterpenos Policíclicos/química , Antibacterianos/farmacologia , Antibacterianos/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Escherichia coli/efeitos dos fármacos , Fungos/efeitos dos fármacos , Bactérias/efeitos dos fármacosRESUMO
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.
Assuntos
Ceratite por Acanthamoeba , Emulsões , Sesquiterpenos Policíclicos , Ceratite por Acanthamoeba/tratamento farmacológico , Ceratite por Acanthamoeba/parasitologia , Sesquiterpenos Policíclicos/química , Nanopartículas , Administração Oftálmica , Cetrimônio/química , Animais , Acanthamoeba/efeitos dos fármacos , Estabilidade de Medicamentos , Tamanho da Partícula , Soluções Oftálmicas , HumanosRESUMO
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 IC50 values on AChE were 5-36 µg/mL; likewise, the %inh. on AChE (1 µg/cm3 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 (IC50 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%)/ß-selinene (18%)/caryophyllene oxide (10%)-B. simaruba; carotol (44%)/dillapiole (21%)-Pep. pellucida; dillapiole (81% confirmed by 1H-/13C-NMR)-P. holtonii; mint furanone derivative (14%)/mint furanone (14%)-B. graveolens-bark; limonene (17%)/carvone (10%)-B. graveolens-leaves.
Assuntos
Inibidores da Colinesterase , Repelentes de Insetos , Óleos Voláteis , Sesquiterpenos Policíclicos , Animais , Acetilcolinesterase/metabolismo , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/química , Colômbia , Repelentes de Insetos/farmacologia , Repelentes de Insetos/química , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Piper/química , Óleos de Plantas/farmacologia , Óleos de Plantas/química , Sesquiterpenos Policíclicos/química , Sesquiterpenos Policíclicos/farmacologia , Gorgulhos/enzimologia , Gorgulhos/efeitos dos fármacos , Sesquiterpenos de Eudesmano/química , Sesquiterpenos de Eudesmano/farmacologia , Sesquiterpenos/química , Sesquiterpenos/farmacologiaRESUMO
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, ß-pinene, limonene, (E)-caryophyllene, bicyclogermacrene, caryophyllene oxide, germacrene D, spathulenol, and ß-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.
Assuntos
Annonaceae/química , Óleos Voláteis/química , Compostos Fitoquímicos/química , Antibacterianos/química , Antibacterianos/uso terapêutico , Brasil , Humanos , Óleos Voláteis/uso terapêutico , Folhas de Planta/química , Sesquiterpenos Policíclicos/química , Sesquiterpenos/química , Sesquiterpenos de Germacrano/químicaRESUMO
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%), ß-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 SC50 of 901 ± 20 µg/mL with the ABTS method, and very strong antiglucosidase activity with an IC50 of 146 ± 20 µg/mL.
Assuntos
Anti-Infecciosos/química , Antioxidantes/química , Croton/química , Inibidores Enzimáticos/química , Óleos Voláteis/química , Folhas de Planta/química , Monoterpenos Acíclicos/química , Monoterpenos Acíclicos/isolamento & purificação , Alcenos/química , Alcenos/isolamento & purificação , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Benzotiazóis/antagonistas & inibidores , Compostos de Bifenilo/antagonistas & inibidores , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Monoterpenos Cicloexânicos/química , Monoterpenos Cicloexânicos/isolamento & purificação , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Sesquiterpenos Monocíclicos/química , Sesquiterpenos Monocíclicos/isolamento & purificação , Picratos/antagonistas & inibidores , Sesquiterpenos Policíclicos/química , Sesquiterpenos Policíclicos/isolamento & purificação , Sesquiterpenos de Germacrano/química , Sesquiterpenos de Germacrano/isolamento & purificação , Ácidos Sulfônicos/antagonistas & inibidores , alfa-Glucosidases/químicaRESUMO
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% ß-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.
Assuntos
Abelhas/química , Própole/química , Compostos Orgânicos Voláteis/química , Animais , Brasil , Cromatografia Gasosa-Espectrometria de Massas/métodos , Hidrocarbonetos/química , Sesquiterpenos Policíclicos/química , Resinas Vegetais/química , Sesquiterpenos/químicaRESUMO
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, ß-Pinene, δ-3-Carene, α-Pinene, (E)-Caryophyllene, Guaiol, and ß-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 IC50 values of 38.2 ± 2.9 µg/mL and 47.4 ± 2.3 µg/mL, respectively.
Assuntos
Acetilcolinesterase/química , Butirilcolinesterase/química , Inibidores da Colinesterase/farmacologia , Lamiaceae/efeitos dos fármacos , Óleos Voláteis/química , Extratos Vegetais/química , Folhas de Planta/química , Monoterpenos Cicloexânicos/química , Eucaliptol/química , Flores/química , Cromatografia Gasosa-Espectrometria de Massas , Hidrocarbonetos , Concentração Inibidora 50 , Sesquiterpenos Policíclicos/química , Sesquiterpenos de Guaiano/química , EstereoisomerismoRESUMO
BACKGROUND: Central nervous system disorders such as anxiety, depression and epilepsy are characterized by sharing several molecular mechanisms in common and the involvement of the L-arginine/NO pathway in neurobehavioral studies with ß-caryophyllene is still little discussed. OBJECTIVES: One of the objectives of the present study was to demonstrate the anxiolytic behavioral effect of ß-caryophyllene (ß-CBP) in female Swiss mice, as well as to investigate the molecular mechanisms underlying the results obtained. METHODS: This study evaluated the neurobehavioral effects of ß-CBP using the open field test, rota- rod test, elevated plus maze test, novelty suppressed feeding test, tail suspension test and forced swim test, as well as pilocarpine, pentylenetetrazole and isoniazid-induced epileptic seizure models. RESULTS: The results demonstrated that the neuropharmacological activities of ß-CBP may involve benzodiazepine/GABAergic receptors, since the pre-treatment of ß-CBP (200 mg/kg) associated with flumazenil (5 mg/kg, benzodiazepine receptor antagonist) and bicuculline (1 mg/kg, selective GABAA receptor antagonist) reestablished the anxiety parameters in the elevated plus-maze test, as well as the results of reduced latency to consume food in the novelty suppressed feeding test. In addition to benzodiazepine/GABAergic receptors, the neuropharmacological properties of ß-CBP may be related to inhibition of nitric oxide synthesis, since pre-treatment with L-arginine (500-750 mg/kg) reversed significantly the anxiolytic, antidepressant and anticonvulsant activities of ß-CBP. CONCLUSION: The results obtained provide additional support in understanding the neuromolecular mechanisms underlying the anxiolytic, antidepressant and anticonvulsive properties of ß-CBP in female Swiss mice.
Assuntos
Ansiolíticos/química , Anticonvulsivantes/química , Antidepressivos/química , Antagonistas de Receptores de GABA-A/química , Sesquiterpenos Policíclicos/química , Animais , Ansiolíticos/farmacologia , Anticonvulsivantes/farmacologia , Antidepressivos/farmacologia , Arginina , Comportamento Animal , Benzodiazepinas/metabolismo , Bicuculina/química , Bicuculina/farmacologia , Feminino , Flumazenil/química , Flumazenil/farmacologia , Antagonistas de Receptores de GABA-A/farmacologia , Humanos , Aprendizagem em Labirinto , Camundongos , Óxido Nítrico/metabolismo , Sesquiterpenos Policíclicos/farmacologia , Receptores de GABA-A/metabolismo , Convulsões/induzido quimicamente , Transdução de SinaisRESUMO
The vascular endothelium is a continuous monolayer of endothelial cells that are in direct contact with the blood and its dysfunction is the starting process in the development of many pathological inflammatory disorders, such as atherosclerosis, which can result in death. The expression of adhesion molecules such as vascular cell adhesion molecule 1 (VCAM1) and intercellular adhesion molecule 1 (ICAM1) is a key stage in modulating vascular inflammation, where the adhesion of monocytes and their transmigration into the intima starting a cascade of inflammatory reactions. Looking for natural compounds with inhibitory activity of VCAM1 and ICAM1, we isolated drimenol, isodrimeninol and polygodial as the main secondary metabolites from barks of Drimys winteri (Dw) and evaluated their effects in the adhesion response of monocytes cells (THP1) to a monolayer of human umbilical vein endothelial cells (HUVEC) in coculture assays. The results showed that the molecules and total extract Dw decrease the adhesion of THP1 to HUVECs, at 10 µg/mL. The adhesion activity is explained due to the inhibition of VCAM1 and ICAM1 evidenced by qRT-PCR and Western-blot assays. In conclusion, drimane sesquiterpenoids could be used as a molecular scaffold in the development of drugs for inflammatory vascular diseases.
Assuntos
Adesão Celular/efeitos dos fármacos , Drimys/química , Endotélio Vascular/efeitos dos fármacos , Monócitos/efeitos dos fármacos , Sesquiterpenos Policíclicos/farmacologia , Sesquiterpenos/farmacologia , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Monócitos/citologia , Sesquiterpenos Policíclicos/química , Sesquiterpenos Policíclicos/isolamento & purificação , Sesquiterpenos/isolamento & purificaçãoRESUMO
Candida species cause an opportunistic yeast infection called Candidiasis, which is responsible for more than 50,000 deaths every year around the world. Effective treatments against candidiasis caused by non-albicans Candida species such as C. glabrata, C. parapsilosis, C. aureus, and C.krusei are limited due to severe resistance to conventional antifungal drugs. Natural drimane sesquiterpenoids have shown promising antifungal properties against Candida yeast and have emerged as valuable candidates for developing new candidiasis therapies. In this work, we isolated isodrimeninol (C1) from barks of Drimys winteri and used it as starting material for the hemi-synthesis of four sesquiterpenoids by oxidation with pyridinium chlorochromate (PCC). The structure of the products (C2, C3, C4, and C5) was elucidated by 1D and 2D NMR spectroscopy resulting in C4 being a novel compound. Antifungal activity assays against C. albicans, C. glabrata, and C. krusei revealed that C4 exhibited an increased activity (IC50 of 75 µg/mL) compared to C1 (IC50 of 125 µg/mL) in all yeast strains. The antifungal activity of C1 and C4 was rationalized in terms of their capability to inhibit lanosterol 14-alpha demethylase using molecular docking, molecular dynamics simulations, and MM/GBSA binding free energy calculations. In silico analysis revealed that C1 and C4 bind to the outermost region of the catalytic site of 14-alpha demethylase and block the entrance of lanosterol (LAN) to the catalytic pocket. Binding free energy estimates suggested that C4 forms a more stable complex with the enzyme than C1, in agreement with the experimental evidence. Based on this new approach it is possible to design new drimane-type sesquiterpenoids for the control of Candida species as inhibitors of 14-alpha demethylase.
Assuntos
Inibidores de 14-alfa Desmetilase/química , Candida/crescimento & desenvolvimento , Sesquiterpenos Policíclicos/química , Compostos de Piridínio/química , Sesquiterpenos/química , Esterol 14-Desmetilase/química , Inibidores de 14-alfa Desmetilase/síntese química , Inibidores de 14-alfa Desmetilase/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Antifúngicos/farmacologia , Candida/classificação , Candida/efeitos dos fármacos , Domínio Catalítico , Humanos , Espectroscopia de Ressonância Magnética , Simulação de Acoplamento Molecular , Estrutura Molecular , Oxirredução , Sesquiterpenos Policíclicos/síntese química , Sesquiterpenos Policíclicos/farmacologia , Domínios Proteicos , Compostos de Piridínio/metabolismo , Sesquiterpenos/síntese química , Sesquiterpenos/farmacologia , Esterol 14-Desmetilase/metabolismoRESUMO
Tagetes lucida Cav. (Asteraceae) is an ancient medicinal plant commonly used to alleviate pain. Nevertheless, scientific studies validating this property are lacking in the literature. Animal models of pain were used to evaluate the antinociceptive and anti-inflammatory activities of T. lucida essential oil (TLEO) and a bioactive metabolite. The chemical constitution and possible toxicity of the extract and the mechanism of action of ß-caryophyllene were also explored. Temporal course curves and dose-response graphics were generated using TLEO (0.1-10 mg/kg or 3.16-31.62 mg/kg) and ß-caryophyllene (3.16-10 mg/kg). Metamizole (80 mg/kg) and indomethacin (20 mg/kg) were used as reference drugs in the formalin assay and writhing test in rats and mice, respectively. The ß-caryophyllene mechanism of action was explored in the presence of naloxone (1 mg/kg), flumazenil (10 mg/kg), WAY100635 (0.16 mg/kg), or nitro-l-arginine methyl ester (L-NAME) (20 mg/kg) in the formalin test in rats. GC/MS analysis demonstrated the presence of geranyl acetate (49.89%), geraniol (7.92%), and ß-caryophyllene (6.27%). Significant and dose-dependent antinociceptive response was produced by TLEO and ß-caryophyllene without the presence of gastric damage. In conclusion, ß-caryophyllene was confirmed as a bioactive compound in the T. lucida analgesic properties by involving the participation of receptors like opioids, benzodiazepines, and Serotonin 1A receptor (5-HT1A), as well as nitric oxide.
Assuntos
Anti-Inflamatórios/administração & dosagem , Óleos Voláteis/química , Dor/tratamento farmacológico , Sesquiterpenos Policíclicos/administração & dosagem , Tagetes/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Dipirona/administração & dosagem , Dipirona/farmacologia , Modelos Animais de Doenças , Cromatografia Gasosa-Espectrometria de Massas , Indometacina/administração & dosagem , Indometacina/farmacologia , Masculino , Camundongos , Óxido Nítrico/metabolismo , Dor/metabolismo , Óleos de Plantas/química , Sesquiterpenos Policíclicos/química , Sesquiterpenos Policíclicos/farmacologia , Ratos , Receptor 5-HT1A de Serotonina/metabolismoRESUMO
Paraconiothins A-J (1-10), 10 new sesquiterpenoids, as well as five known sesquiterpenoids, were isolated from the cultures of the endophytic fungus Paraconiothyrium brasiliense ECN-258. The structures of the sesquiterpenoids were elucidated by extensive spectroscopic analysis. Furthermore, the absolute structures of 7 and 8 were determined by comparing their experimental and computed electronic circular dichroism data. Paraconiothins A-G (1-7) were eremophilane sesquiterpenoids, while paraconiothins H-J (8-10) had new or rare carbon frameworks that are possibly biosynthesized by a pathway involving the rearrangement of eremophilane sesquiterpenoids. Paraconiothins C (3) and I (9) exhibited an inhibitory effect on the liver X receptor α at a concentration of 50 µM.
Assuntos
Ascomicetos/química , Sesquiterpenos Policíclicos/isolamento & purificação , Estrutura Molecular , Sesquiterpenos Policíclicos/química , Sesquiterpenos Policíclicos/farmacologia , Análise Espectral/métodosRESUMO
Sensitizing activities exerted by 3,4-dihydro-7-hydroxycadalene (1), rac-3,7-dihydroxy-3(4H)-isocadalen-4-one (4) and (1R,4R)-4H-1,2,3,4-tetrahydro-1-hydroxycadalen-15-oic acid (9), the major cadinanes isolated from Heterotheca inuloides, towards multidrug-resistant MES-SA/MX2 and parental MES-SA epithelial human uterine sarcoma cell lines were evaluated. We also evaluated the in silico interactions (expressed as ΔGbinding in kcal/mol) of cadinanes 1, 4 and 9 in an in vitro assay, and also tested several structurally related natural compounds with the multidrug resistance protein (MDR1, P-glycoprotein), human multidrug resistance protein 1 (MRP1), and breast cancer resistance protein (BCRP) structures as pharmacological targets using AutoDock and AutoDock Vina. Compound 1 potentiated the cytotoxicity of doxorubicin and mitoxantrone drugs in resistant MES-SA/MX2 cells, compared to cells treated with each drug alone. Compound 1 could reverse the resistance to doxorubicin 12.44 fold at a concentration of 5⯵M. It also re-sensitized cells to mitoxantrone 3.94 fold. Hence, compound 1 may be considered as a potential chemosensitizing agent to overcome multidrug resistance in cancer. The docking analysis suggested that there are interactions between cadinanes from H. inuloides and MDR1, MRP1, and BCRP proteins mainly through π-π interactions and hydrogen bonds.