RESUMO
This study evaluated the chemical compositions of the leaves and fruits of eight black pepper cultivars cultivated in Pará State (Amazon, Brazil). Hydrodistillation and gas chromatography-mass spectrometry were employed to extract and analyze the volatile compounds, respectively. Sesquiterpene hydrocarbons were predominant (58.5-90.9%) in the cultivars "Cingapura", "Equador", "Guajarina", "Iaçará", and "Kottanadan", and "Bragantina", "Clonada", and "Uthirankota" displayed oxygenated sesquiterpenoids (50.6-75.0%). The multivariate statistical analysis applied using volatile composition grouped the samples into four groups: γ-Elemene, curzerene, and δ-elemene ("Equador"/"Guajarina", I); δ-elemene ("Iaçará"/"Kottanadan"/"Cingapura", II); elemol ("Clonada"/"Uthirankota", III) and α-muurolol, bicyclogermacrene, and cubebol ("Bragantina", IV). The major compounds in all fruit samples were monoterpene hydrocarbons such as α-pinene, ß-pinene, and limonene. Among the cultivar leaves, phenolics content (44.75-140.53 mg GAE·g-1 FW), the enzymatic activity of phenylalanine-ammonia lyase (20.19-57.22 µU·mL-1), and carotenoids (0.21-2.31 µg·mL-1) displayed significant variations. Due to black pepper's susceptibility to Fusarium infection, a molecular docking analysis was carried out on Fusarium protein targets using each cultivar's volatile components. F. oxysporum endoglucanase was identified as the preferential protein target of the compounds. These results can be used to identify chemical markers related to the susceptibility degree of black pepper cultivars to plant diseases prevalent in Pará State.
Assuntos
Piper nigrum/metabolismo , Sesquiterpenos/análise , Sesquiterpenos/metabolismo , Brasil , Frutas/química , Frutas/genética , Cromatografia Gasosa-Espectrometria de Massas/métodos , Metaboloma , Simulação de Acoplamento Molecular , Monoterpenos/análise , Monoterpenos/metabolismo , Óleos Voláteis/química , Piper nigrum/genética , Folhas de Planta/genética , Óleos de Plantas/química , Sesquiterpenos/químicaRESUMO
Essential oils have shown promise as antiviral agents against several pathogenic viruses. In this work we hypothesized that essential oil components may interact with key protein targets of the 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A molecular docking analysis was carried out using 171 essential oil components with SARS-CoV-2 main protease (SARS-CoV-2 Mpro), SARS-CoV-2 endoribonucleoase (SARS-CoV-2 Nsp15/NendoU), SARS-CoV-2 ADP-ribose-1â³-phosphatase (SARS-CoV-2 ADRP), SARS-CoV-2 RNA-dependent RNA polymerase (SARS-CoV-2 RdRp), the binding domain of the SARS-CoV-2 spike protein (SARS-CoV-2 rS), and human angiotensin-converting enzyme (hACE2). The compound with the best normalized docking score to SARS-CoV-2 Mpro was the sesquiterpene hydrocarbon (E)-ß-farnesene. The best docking ligands for SARS-CoV Nsp15/NendoU were (E,E)-α-farnesene, (E)-ß-farnesene, and (E,E)-farnesol. (E,E)-Farnesol showed the most exothermic docking to SARS-CoV-2 ADRP. Unfortunately, the docking energies of (E,E)-α-farnesene, (E)-ß-farnesene, and (E,E)-farnesol with SARS-CoV-2 targets were relatively weak compared to docking energies with other proteins and are, therefore, unlikely to interact with the virus targets. However, essential oil components may act synergistically, essential oils may potentiate other antiviral agents, or they may provide some relief of COVID-19 symptoms.
Assuntos
Infecções por Coronavirus/terapia , Óleos Voláteis/uso terapêutico , Pneumonia Viral/terapia , Proteínas Virais/metabolismo , Enzima de Conversão de Angiotensina 2 , Antivirais/farmacologia , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , COVID-19 , Simulação por Computador , Humanos , Simulação de Acoplamento Molecular , Óleos Voláteis/farmacologia , Pandemias , Peptidil Dipeptidase A/metabolismo , Ligação Proteica/efeitos dos fármacos , SARS-CoV-2 , Proteínas Virais/químicaRESUMO
During the past five years, the three-dimensional structures of 14 different G-protein coupled receptors (GPCRs) have been resolved by X-ray crystallography. The most recently published structures, those of the opioid receptors (ORs), are remarkably important in pain modulation, drug addiction, and mood disorders. These structures, confirmed previously proposed key interactions conferring potency and antagonistic properties, including the well-known interaction with Asp138, conserved in all aminergic GPCRs. In addition, crystallization of the opioid receptors highlighted the potential function of the ECL2 and ICL2 loops. We have previously reported a set of potent and selective kappa opioid receptor peptide agonists, of which ff(D-nle)r-NH2 is among the most potent and selective ones. These peptides were identified from the deconvolution of a 6,250,000 tetrapeptide combinatorial library. A derivative of this set is currently the subject of a phase 2 clinical trial in the United States. In this work, we describe comparative molecular modeling studies of kappa-OR peptide agonists with the co-crystallized antagonist, JDTic, and also report structure-activity relationships of 23 tetrapeptides. The overall binding and contact interactions are sound and interactions known to favor selectivity and potency were observed. Additional modeling studies will reveal conformational changes that the kappa-OR undergoes upon binding to these peptide agonists.