RESUMO
In the current study, both the essential oil composition and biological activity of Saussurea lappa and Ligusticum sinensis were investigated by means of microwave-assisted hydrodistillation (MAHD) and characterized by Gas chromatography/mass spectrometry (GC/MS), whereas the antimicrobial efficiency of MAHD essential oils was examined against four pathogens: Staphylococcus aureus, Escherichia coli, Aspergillus niger, and Candida albicans responsible for microbial infections. The goal was to spot synergy and a favorable method that gives essential oils to possibly use as alternatives to common antimicrobial agents for the treatment of bacterial infections using a microdilution assay. S. lappa's 21 compounds were characterized by MAHD extraction. Sesquiterpene lactones (39.7 % MAHD) represented the major components, followed by sesquiterpene dialdehyde (25.50 % MAHD), while L. sinensis's 14 compounds were identified by MAHD extraction. Tetrahydroisobenzofurans (72.94 % MAHD) was the predominant compound class. S. lappa essential oil collection showed the strongest antimicrobial activity with MIC values of 16â µg/ml against all pathogens tested, while L. sinensis showed strong antibacterial activity and moderate antifungal activity with MIC values of 32â µg/ml and 500â µg/ml, respectively. The principal components of both oils, (velleral, eremanthin and neocnidilide), were docked into the bacterial histidine kinase (HK) and the fungal heat shock protein 90 (Hsp90).
Assuntos
Anti-Infecciosos , Ligusticum , Óleos Voláteis , Saussurea , Sesquiterpenos , Óleos Voláteis/química , Simulação de Acoplamento Molecular , Micro-Ondas , Antibacterianos/farmacologia , Antibacterianos/química , Testes de Sensibilidade MicrobianaRESUMO
Centaurea is a genus compromising over 250 herbaceous flowering species and is used traditionally to treat several ailments. Among the Egyptian Centaurea species, C. lipii was reported to be cytotoxic against multidrug-resistant cancer cells. In this context, we aimed to explore the metabolome of C. lipii and compare it to other members of the genus in pursuance of identifying its bioactive principles. An LC-MS/MS analysis approach synchronized with feature-based molecular networks was adopted to offer a holistic overview of the metabolome diversity of the Egyptian Centaurea species. The studied plants included C. alexandrina, C. calcitrapa, C. eryngioides, C. glomerata, C. lipii, C. pallescens, C. pumilio, and C. scoparia. Their constitutive metabolome showed diverse chemical classes such as cinnamic acids, sesquiterpene lactones, flavonoids, and lignans. Linking the recorded metabolome to the previously reported cytotoxicity identified sesquiterpene lactones as the major contributors to this activity. To confirm our findings, bioassay-guided fractionation of C. lipii was adopted and led to the isolation of the sesquiterpene lactone cynaropicrin with an IC50 of 1.817 µM against the CCRF-CEM leukemia cell line. The adopted methodology highlighted the uniqueness of the constitutive metabolome of C. lipii and determined the sesquiterpene lactones to be the responsible cytotoxic metabolites.
Assuntos
Antineoplásicos , Centaurea , Sesquiterpenos , Extratos Vegetais/química , Cromatografia Líquida , Resistência a Múltiplos Medicamentos , Egito , Resistencia a Medicamentos Antineoplásicos , Espectrometria de Massas em Tandem , Centaurea/química , Compostos Fitoquímicos/farmacologia , Sesquiterpenos/química , Lactonas/químicaRESUMO
Soft corals are recognized as an abundant source of diverse secondary metabolites with unique chemical features and physiologic capabilities. However, the discovery of these metabolites is usually hindered by the traditional protocol which requires a large quantity of living tissue for isolation and spectroscopic investigations. In order to overcome this problem, untargeted metabolomics protocols have been developed. The latter have been applied here to study the chemodiversity of common Egyptian soft coral species, using only minute amounts of coral biomass. Spectral similarity networks, based on high-resolution tandem mass spectrometry data, were employed to explore and highlight the metabolic biodiversity of nine Egyptian soft coral species. Species-specific metabolites were highlighted for future prioritization of soft coral species for MS-guided chemical investigation. Overall, 79 metabolites were tentatively assigned, encompassing diterpenes, sesquiterpenes, and sterols. Simultaneously, the methodology assisted in shedding light on newly-overlooked chemical diversity with potential undescribed scaffolds. For instance, glycosylated fatty acids, nitrogenated aromatic compounds, and polyketides were proposed in Sinularia leptoclados, while alkaloidal terpenes and N-acyl amino acids were proposed in both Sarcophyton roseum and Sarcophyton acutum.
Assuntos
Antozoários , Diterpenos , Policetídeos , Sesquiterpenos , Animais , Oceano Índico , Egito , Antozoários/química , Metaboloma , Diterpenos/química , Esteróis/metabolismo , Terpenos/metabolismo , Policetídeos/metabolismo , Aminoácidos/metabolismo , Ácidos Graxos/metabolismo , CatalogaçãoRESUMO
Natural products and chemical analogues are widely used in drug discovery, notably in cancer and infectious disease pharmacotherapy. Sarcophyton convolutum (Alcyoniidae) a Red Sea-derived soft coral has been shown to be a rich source of macrocyclic diterpenes and cyclized derivatives. Two previously undescribed polyoxygenated cembrane-type diterpenoids, sarcoconvolutums F (1) and G (2), as well as four identified analogues (3-6) together with a furan derivate (7) were isolated from a solvent extract. Compounds were identified by spectroscopic techniques, including NMR, HREIMS, and CD, together with close spectral comparisons of previously published data. Sarcoconvolutum F (1) contains a rare 1-peroxid-15-hydroxy-10-ene functionality. Isolated metabolites (1-7) were screened against lung adenocarcinoma (A549), cervical cancer (HeLa) and oral cavity carcinoma (HSC-2) lines. Compound 4 exhibited an IC50 56 µM and 55 µM against A549 and HSC-2 cells, respectively.
Assuntos
Antozoários , Produtos Biológicos , Diterpenos , Animais , Antozoários/química , Produtos Biológicos/farmacologia , Diterpenos/química , Diterpenos/farmacologia , Furanos , Oceano Índico , Estrutura Molecular , SolventesRESUMO
The soft coral genus Sarcophyton contains the enzymatic machinery to synthesize a multitude of cembrene-type diterpenes. Herein, highly oxygenated cembrenoids, sarcoconvolutum A-E (1-5) were purified and characterized from an ethyl acetate extract of the red sea soft coral, Sarcophyton convolutum. Compounds were assemblies according to spectroscopic methods including FTIR, 1D- and 2D-NMR as well as HRMS. Metabolite cytotoxicity was tested against lung adenocarcinoma, cervical cancer, and oral-cavity carcinoma (A549, HeLa and HSC-2, respectively). The most cytotoxic compound, (4) was observed to be active against cell lines A549 and HSC-2 with IC50 values of 49.70 and 53.17 µM, respectively.
Assuntos
Antozoários , Antineoplásicos/farmacologia , Diterpenos/farmacologia , Animais , Organismos Aquáticos , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Oceano Índico , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Relação Estrutura-AtividadeRESUMO
The coronavirus pandemic has affected more than 150 million people, while over 3.25 million people have died from the coronavirus disease 2019 (COVID-19). As there are no established therapies for COVID-19 treatment, drugs that inhibit viral replication are a promising target; specifically, the main protease (Mpro) that process CoV-encoded polyproteins serves as an Achilles heel for assembly of replication-transcription machinery as well as down-stream viral replication. In the search for potential antiviral drugs that target Mpro, a series of cembranoid diterpenes from the biologically active soft-coral genus Sarcophyton have been examined as SARS-CoV-2 Mpro inhibitors. Over 360 metabolites from the genus were screened using molecular docking calculations. Promising diterpenes were further characterized by molecular dynamics (MD) simulations based on molecular mechanics-generalized Born surface area (MM-GBSA) binding energy calculations. According to in silico calculations, five cembranoid diterpenes manifested adequate binding affinities as Mpro inhibitors with ΔGbinding < -33.0 kcal/mol. Binding energy and structural analyses of the most potent Sarcophyton inhibitor, bislatumlide A (340), was compared to darunavir, an HIV protease inhibitor that has been recently subjected to clinical-trial as an anti-COVID-19 drug. In silico analysis indicates that 340 has a higher binding affinity against Mpro than darunavir with ΔGbinding values of -43.8 and -34.8 kcal/mol, respectively throughout 100 ns MD simulations. Drug-likeness calculations revealed robust bioavailability and protein-protein interactions were identified for 340; biochemical signaling genes included ACE, MAPK14 and ESR1 as identified based on a STRING database. Pathway enrichment analysis combined with reactome mining revealed that 340 has the capability to re-modulate the p38 MAPK pathway hijacked by SARS-CoV-2 and antagonize injurious effects. These findings justify further in vivo and in vitro testing of 340 as an antiviral agent against SARS-CoV-2.
Assuntos
Antozoários/química , Tratamento Farmacológico da COVID-19 , Proteases 3C de Coronavírus/antagonistas & inibidores , Inibidores de Protease de Coronavírus/farmacologia , Diterpenos/farmacologia , SARS-CoV-2/efeitos dos fármacos , Animais , COVID-19/virologia , Proteases 3C de Coronavírus/metabolismo , Inibidores de Protease de Coronavírus/química , Inibidores de Protease de Coronavírus/isolamento & purificação , Diterpenos/química , Diterpenos/isolamento & purificação , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Molecular , SARS-CoV-2/enzimologia , SARS-CoV-2/patogenicidade , Relação Estrutura-AtividadeRESUMO
Centaurothamnus maximus (family Asteraceae), is a leafy shrub indigenous to the southwestern Arabian Peninsula. With a paucity of phytochemical data on this species, we set out to chemically characterize the plant. From the aerial parts, two newly identified guaianolides were isolated: 3ß-hydroxy-4α(acetoxy)-4ß(hydroxymethyl)-8α-(4-hydroxy methacrylate)-1αH,5αH, 6αH-gual-10(14),11(13)-dien-6,12-olide (1) and 15-descarboxy picrolide A (2). Seven previously reported compounds were also isolated: 3ß, 4α, 8α-trihydroxy-4-(hydroxymethyl)-lαH, 5αH, 6ßH, 7αH-guai-10(14),11(13)-dien-6,12-olide (3), chlorohyssopifolin B (4), cynaropikrin (5), hydroxyjanerin (6), chlorojanerin (7), isorhamnetin (8), and quercetagetin-3,6-dimethyl ether-4'-O-ß-d-pyranoglucoside (9). Chemical structures were elucidated using spectroscopic techniques, including High Resolution Fast Atom Bombardment Mass Spectrometry (HR-FAB-MS), 1D NMR; 1H, 13C NMR, Distortionless Enhancement by Polarization Transfer (DEPT), and 2D NMR (1H-1H COSY, HMQC, HMBC) analyses. In addition, a biosynthetic pathway for compounds 1-9 is proposed. The chemotaxonomic significance of the reported sesquiterpenoids and flavonoids considering reports from other Centaurea species is examined.
Assuntos
Asteraceae/química , Lactonas/isolamento & purificação , Sesquiterpenos de Guaiano/isolamento & purificação , Vias Biossintéticas , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Flavonas/química , Flavonas/isolamento & purificação , Lactonas/química , Conformação Molecular , Espectroscopia de Prótons por Ressonância Magnética , Sesquiterpenos de Guaiano/químicaRESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent for the COVID-19 pandemic, which generated more than 1.82 million deaths in 2020 alone, in addition to 83.8 million infections. Currently, there is no antiviral medication to treat COVID-19. In the search for drug leads, marine-derived metabolites are reported here as prospective SARS-CoV-2 inhibitors. Two hundred and twenty-seven terpene natural products isolated from the biodiverse Red-Sea ecosystem were screened for inhibitor activity against the SARS-CoV-2 main protease (Mpro) using molecular docking and molecular dynamics (MD) simulations combined with molecular mechanics/generalized Born surface area binding energy calculations. On the basis of in silico analyses, six terpenes demonstrated high potency as Mpro inhibitors with ΔGbinding ≤ -40.0 kcal/mol. The stability and binding affinity of the most potent metabolite, erylosides B, were compared to the human immunodeficiency virus protease inhibitor, lopinavir. Erylosides B showed greater binding affinity towards SARS-CoV-2 Mpro than lopinavir over 100 ns with ΔGbinding values of -51.9 vs. -33.6 kcal/mol, respectively. Protein-protein interactions indicate that erylosides B biochemical signaling shares gene components that mediate severe acute respiratory syndrome diseases, including the cytokine- and immune-signaling components BCL2L1, IL2, and PRKC. Pathway enrichment analysis and Boolean network modeling were performed towards a deep dissection and mining of the erylosides B target-function interactions. The current study identifies erylosides B as a promising anti-COVID-19 drug lead that warrants further in vitro and in vivo testing.
Assuntos
Invertebrados/química , SARS-CoV-2/metabolismo , Terpenos/química , Proteínas da Matriz Viral/antagonistas & inibidores , Animais , Sítios de Ligação , COVID-19/virologia , Humanos , Ligação de Hidrogênio , Invertebrados/metabolismo , Lopinavir/química , Lopinavir/metabolismo , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Inibidores de Proteases/química , Inibidores de Proteases/isolamento & purificação , Inibidores de Proteases/uso terapêutico , Ligação Proteica , SARS-CoV-2/isolamento & purificação , Terpenos/isolamento & purificação , Terpenos/metabolismo , Terpenos/uso terapêutico , Termodinâmica , Proteínas da Matriz Viral/metabolismo , Tratamento Farmacológico da COVID-19RESUMO
Structurally diverse natural products are valued for their targeted biological activity. The challenge of working with such metabolites is their low natural abundance and complex structure, often with multiple stereocenters, precludes large-scale or unsophisticated chemical synthesis. Since select plants contain the enzymatic machinery necessary to produce specialized compounds, tissue cultures can be used to achieve key transformations for large-scale chemical and/or pharmaceutical applications. In this context, plant tissue-culture bio-transformations have demonstrated great promise in the preparation of pharmaceutical products. This review describes the capacity of cultured plant cells to transform terpenoid natural products and the specific application of such transformations over the past three decades (1988-2019).
Assuntos
Plantas/metabolismo , Terpenos/metabolismo , Biotransformação , Técnicas de Cultura de Células , Estruturas Vegetais/metabolismoRESUMO
Plants are considered green resources for thousands of bioactive compounds. Essential oils (EOs) are an important class of secondary compounds with various biological activities, including allelopathic and antimicrobial activities. Herein, the present study aimed to compare the chemical profiles of the EOs of the widely distributed medicinal plant Calotropis procera collected from Saudi Arabia and Egypt. In addition, this study also aimed to assess their allelopathic and antimicrobial activities. The EOs from Egyptian and Saudi ecospecies were extracted by hydrodistillation and analyzed via GC-MS. The correlation between the analyzed EOs and those published from Egypt, India, and Nigeria was assessed by principal component analysis (PCA) and agglomerative hierarchical clustering (AHC). The allelopathic activity of the extracted EOs was tested against two weeds (Bidens pilosa and Dactyloctenium aegyptium). Moreover, the EOs were tested for antimicrobial activity against seven bacterial and two fungal strains. Ninety compounds were identified from both ecospecies, where 76 compounds were recorded in Saudi ecospecies and 33 in the Egyptian one. Terpenes were recorded as the main components along with hydrocarbons, aromatics, and carotenoids. The sesquiterpenes (54.07%) were the most abundant component of EO of the Saudi sample, while the diterpenes (44.82%) represented the mains of the Egyptian one. Hinesol (13.50%), trans-chrysanthenyl acetate (12.33%), 1,4-trans-1,7-cis-acorenone (7.62%), phytol (8.73%), and myristicin (6.13%) were found as the major constituents of EO of the Saudi sample, while phytol (38.02%), n-docosane (6.86%), linoleic acid (6.36%), n-pentacosane (6.31%), and bicyclogermacrene (4.37%) represented the main compounds of the Egyptian one. It was evident that the EOs of both ecospecies had potent phytotoxic activity against the two tested weeds, while the EO of the Egyptian ecospecies was more effective, particularly on the weed D. aegyptium. Moreover, the EOs showed substantial antibacterial and antifungal activities. The present study revealed that the EOs of Egyptian and Saudi ecospecies were different in quality and quantity, which could be attributed to the variant environmental and climatic conditions. The EOs of both ecospecies showed significant allelopathic and antimicrobial activity; therefore, these EOs could be considered as potential green eco-friendly resources for weed and microbe control, considering that this plant is widely grown in arid habitats.
Assuntos
Alelopatia , Anti-Infecciosos/química , Bidens/efeitos dos fármacos , Calotropis/química , Óleos Voláteis/química , Poaceae/efeitos dos fármacos , Antioxidantes/química , Análise por Conglomerados , Ecossistema , Egito , Cromatografia Gasosa-Espectrometria de Massas , Componentes Aéreos da Planta/química , Extratos Vegetais/química , Plantas Daninhas/efeitos dos fármacos , Análise de Componente Principal , Arábia Saudita , Terpenos/química , Compostos Orgânicos Voláteis/químicaRESUMO
Cyperus has been commonly used as a multi-use medicinal plant in folk medicine worldwide. The objectives of our study were to determine the different metabolites in the Cyperus conglomeratus Rottb. methanol extract, and to assess its in vivo gastroprotective effect in ethanol-induced gastric ulcer model in rats. Serum levels of galactin-3 and TNF-α were employed as biochemical markers. To pinpoint for active agents, comprehensive metabolites profiling of extract via UPLC-qTOF-MS/MS was employed. A total of 77 chromatographic peaks were detected, of which 70 were annotated. The detected metabolites were categorized into phenolic acids and their derivatives, flavonoids, stilbenes, aurones, quinones, terpenes, and steroids. Rats were divided into six groups; healthy control, ulcer control, standard drug group, and 25, 50, 100 mg/kg of C. conglomeratus treated rats. Pre-treatment with C. conglomeratus alcohol extract significantly reduced galactin-3, and TNF-α in ethanol-induced ulcer model at 25, 50, and 100 mg/kg. Further histopathological and histochemical studies revealed moderate erosion of superficial epithelium, few infiltrated inflammatory cells, and depletion of gastric tissue glycoprotein in the ulcer group. Treatment with the extract protected the gastric epithelial cells in a dose-dependent manner. It could be concluded that C. conglomeratus extract provides significant gastroprotective activity in ethanol-induced gastric ulcer and ought to be included in nutraceuticals in the future for ulcer treatment.
Assuntos
Antiulcerosos/química , Cyperus/química , Compostos Fitoquímicos/química , Extratos Vegetais/química , Administração Oral , Animais , Antiulcerosos/farmacologia , Antiulcerosos/uso terapêutico , Cromatografia Líquida de Alta Pressão , Cyperus/metabolismo , Etanol/toxicidade , Feminino , Galectina 3/sangue , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Componentes Aéreos da Planta/química , Componentes Aéreos da Planta/metabolismo , Ranitidina/uso terapêutico , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/patologia , Espectrometria de Massas em Tandem , Fator de Necrose Tumoral alfa/sangueRESUMO
Euphorbia species were widely used in traditional medicines for the treatment of several diseases. From the aerial parts of Egyptian endemic plant, Euphorbia sanctae-catharinae, three new premyrsinane diterpenoids, namely, euphosantianane E-G (1-3), alongside four known triterpenes, 9,19-cyclolanostane-3ß,24S-diol (4), 25-methoxycycloartane-3ß,24S-diol (5), 25-methylenecycloartan-3ß,24R-diol (6), and 25-methylenecycloartan-3ß,24S-diol (7), were isolated and identified. The chemical structures were proven depending upon spectroscopic analysis, including FTIR, HRFABMS, and 1D/2D-NMR. The chemotaxonomic significance of the isolated compounds, especially diterpenes from E. sanctae-catharinae compared to those documented from different Euphorbia species was also studied via agglomerative hierarchical clustering (AHC). The Egyptian endemic Euphorbia sanctae-catharina was grouped with E. bupleuroides, E. fidjiana, E. fischeriana, E. pithyusa subsp. cupanii, E. prolifera, and E. seguieriana, where myrsinol diterpenoids were the characteristic compounds.
Assuntos
Antineoplásicos Fitogênicos/síntese química , Diterpenos/síntese química , Euphorbia/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Diterpenos/química , Diterpenos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Egito , Estrutura Molecular , Componentes Aéreos da Planta/química , Extratos Vegetais/químicaRESUMO
Three new cembrene diterpenoids, sarcoehrenbergilid A-C (1-3), along with four known diterpenoids, sarcophine (4), (+)-7α,8ß-dihydroxydeepoxysarcophine (5), sinulolide A (6), and sinulolide B (7), and one steroid, sardisterol (8), were isolated and characterized from a solvent extract of the Red Sea soft coral Sarcophyton ehrenbergi. Chemical structures were elucidated by NMR and MS analyses with absolute stereochemistry determined by X-ray analysis. Since these isolated cembrene diterpenes contained 10 or more carbons in a large flexible ring, conformer stabilities were examined based on density functional theory calculations. Anti-proliferative activities for 1-8 were evaluated against three human tumor cell lines of different origins including the: lung (A549), colon (Caco-2), and liver (HepG2). Sardisterol (8) was the most potent of the metabolites isolated with an IC50 of 27.3 µM against the A549 cell line. Since an elevated human-cancer occurrence is associated with an aberrant receptor function for the epidermal growth factor receptor (EGFR), molecular docking studies were used to examine preferential metabolite interactions/binding and probe the mode-of-action for metabolite-anti tumor activity.
Assuntos
Antozoários/química , Proliferação de Células/efeitos dos fármacos , Diterpenos/química , Diterpenos/farmacologia , Éter/química , 4-Butirolactona/análogos & derivados , 4-Butirolactona/farmacologia , Células A549 , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Células CACO-2 , Linhagem Celular Tumoral , Células Hep G2 , Humanos , Oceano Índico , Espectroscopia de Ressonância Magnética/métodos , Simulação de Acoplamento MolecularRESUMO
Three new cembrenoids, lobophylins F-H (1-3), along with three known ones, lobophylins A-C (4-6), were isolated from the ethyl acetate extract of the Taiwan water soft coral Lobophytum crassum. The structures of isolated cembrenoids were elucidated on the basis of extensive spectroscopic methods such as IR, 1D, 2D NMR and HR-ESI-MS.
Assuntos
Antozoários/química , Diterpenos/isolamento & purificação , Animais , Diterpenos/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , TaiwanRESUMO
Two new sesquiterpene lactones 3R, 8R-dihydroxygermacr-4(15),9(10)-dien-6S,7S,11RH,12,6-olide (1) and 1R, 8S-dihydroxy-11R,13-dihydrobalchanin(2), together with two known compounds 11-epiartapshin (3) and 3'-hydroxygenkwanin (4), were isolated from Artemisia sieberi. Their structures were elucidated by 1D, 2D NMR, MS, and X-ray diffraction. Compound 4 inhibited Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus with Minimal inhibitory concentration values of 50 and 25 µg/disk, respectively. All the isolated compounds exhibited moderate antifungal activities.
Assuntos
Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Artemisia/química , Asteraceae/química , Lactonas/isolamento & purificação , Lactonas/farmacologia , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Antibacterianos/química , Bacillus subtilis/efeitos dos fármacos , Lactonas/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Extratos Vegetais/química , Sesquiterpenos/química , Staphylococcus aureus/efeitos dos fármacos , EstereoisomerismoRESUMO
Marine life has developed unique metabolic and physiologic capabilities and advanced symbiotic relationships to survive in the varied and complex marine ecosystems. Herein, metabolite composition of the soft coral genus Sarcophyton was profiled with respect to its species and different habitats along the coastal Egyptian Red Sea via (1)H NMR and ultra performance liquid chromatography-mass spectrometry (UPLC-MS) large-scale metabolomics analyses. The current study extends the application of comparative secondary metabolite profiling from plants to corals revealing for metabolite compositional differences among its species via a comparative MS and NMR approach. This was applied for the first time to investigate the metabolism of 16 Sarcophyton species in the context of their genetic diversity or growth habitat. Under optimized conditions, we were able to simultaneously identify 120 metabolites including 65 diterpenes, 8 sesquiterpenes, 18 sterols, and 15 oxylipids. Principal component analysis (PCA) and orthogonal projection to latent structures-discriminant analysis (OPLS) were used to define both similarities and differences among samples. For a compound based classification of coral species, UPLC-MS was found to be more effective than NMR. The main differentiations emanate from cembranoids and oxylipids. The specific metabolites that contribute to discrimination between soft corals of S. ehrenbergi from the three different growing habitats also belonged to cembrane type diterpenes, with aquarium S. ehrenbergi corals being less enriched in cembranoids compared to sea corals. PCA using either NMR or UPLC-MS data sets was found equally effective in predicting the species origin of unknown Sarcophyton. Cyclopropane containing sterols observed in abundance in corals may act as cellular membrane protectant against the action of coral toxins, that is, cembranoids.
Assuntos
Antozoários/química , Diterpenos/isolamento & purificação , Metabolômica , Sesquiterpenos/isolamento & purificação , Esteróis/isolamento & purificação , Animais , Antozoários/metabolismo , Biodiversidade , Cromatografia Líquida de Alta Pressão/métodos , Análise Discriminante , Diterpenos/metabolismo , Egito , Oceano Índico , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Análise de Componente Principal , Metabolismo Secundário , Sesquiterpenos/metabolismo , Esteróis/metabolismoRESUMO
Wild artichoke (Cynara cornigera), a thistle-like perennial belonging to the Asteraceae family, is native to the Mediterranean region, northwestern Africa, and the Canary Islands. While the pleasant, albeit bitter, taste of the leaves and flowers is attributed to the sesquiterpene lactones cynaropicrin and cynarin, a comprehensive phytochemical investigation still needs to be reported. In this study seven sesquiterpene lactones were isolated from an aqueous methanol plant extract, including a new halogenated metabolite (1), the naturally isolated compound sibthorpine (2), and five metabolites isolated for the first time from C. cornigera. Structures were established by spectroscopic methods, including HREIMS, (1 )H, (13 )C, DEPT, (1 )H-(1 )H COSY, HMQC, and HMBC-NMR experiments as well as by X-ray analysis. The isolated bioactive nutrients were analyzed for their antioxidant and metal chelating activity. Compound 1 exhibited a potent metal chelating activity as well as a high antioxidant capacity. Moreover, select compounds were effective as acetyl cholinesterase inhibitors presenting the possibility for such compounds to be examined for anti-neurodegenerative activity. A computational pharmacophore elucidation and docking study was performed to estimate the pharmacophoric features and binding conformation of isolated compounds in the acetyl cholinesterase active site.
Assuntos
Inibidores da Colinesterase/química , Cynara/química , Lactonas/química , Extratos Vegetais/química , Sesquiterpenos/química , África , Antioxidantes/química , Quelantes/química , Inibidores da Colinesterase/isolamento & purificação , Cristalografia por Raios X , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/isolamento & purificação , Lactonas/isolamento & purificação , Estrutura Molecular , Sesquiterpenos/isolamento & purificaçãoRESUMO
The soft coral genus Sinularia is a rich source of bioactive metabolites containing a diverse array of chemical structures. A solvent extract of Sinularia polydactyla resulted in the isolation of three new casbane diterpenes: sinularcasbane M (1), sinularcasbane N (2) and sinularcasbane O (3); in addition, known metabolites (4-5) were isolated. Compounds were elucidated on the basis of spectroscopic analyses; the absolute configuration was confirmed by X-ray analysis.
Assuntos
Antozoários/química , Diterpenos/isolamento & purificação , Animais , Cristalografia por Raios X , Diterpenos/química , Oceano Índico , Espectroscopia de Ressonância Magnética , Estrutura Molecular , SolventesRESUMO
Marine invertebrates including sponges, soft coral, tunicates, mollusks and bryozoan have proved to be a prolific source of bioactive natural products. Among marine-derived metabolites, terpenoids have provided a vast array of molecular architectures. These isoprenoid-derived metabolites also exhibit highly specialized biological activities ranging from nerve regeneration to blood-sugar regulation. As a result, intense research activity has been devoted to characterizing invertebrate terpenes from both a chemical and biological standpoint. This review focuses on the chemistry and biology of terpene metabolites isolated from the Red Sea ecosystem, a unique marine biome with one of the highest levels of biodiversity and specifically rich in invertebrate species.
Assuntos
Produtos Biológicos/química , Produtos Biológicos/farmacologia , Invertebrados/química , Terpenos/química , Terpenos/farmacologia , Animais , Biodiversidade , Ecossistema , Humanos , Oceano ÍndicoRESUMO
Sustained inflammatory responses can badly affect several vital organs and lead to chronic inflammation-related disorders, such as atherosclerosis, pneumonia, rheumatoid arthritis, obesity, diabetes, Alzheimer's disease, and cancers. Salvia multicaulis is one of the widely distributed plants that contains several biologically active phytochemicals and diterpenoids with anti-inflammatory effects. Therefore, finding alternative and safer natural plant-extracted compounds with good curative anti-inflammatory efficiencies is an urgent need for the clinical treatment of inflammation-related diseases. In the current study, S. multicaulis Vahl was used to extract and isolate two compounds identified as salvimulticanol and candesalvone B methyl ester to examine their effects against inflammation in murine macrophage RAW264.7 cells that were induced by lipopolysaccharide (LPS). Accordingly, after culturing RAW264.7 cells and induction of inflammation by LPS (100 ng/ml), cells were exposed to different concentrations (9, 18, 37.5, 75, and 150 µM) of each compound. Then, Griess assay for detection of nitric oxide (NO) levels and western blotting for the determination of inducible nitric oxide synthase (iNOS) expression were performed. Molecular docking and molecular dynamics (MD) simulation studies were employed to investigate the anti-inflammatory mechanism. Our obtained results validated that the level of NO was significantly decreased in the macrophage cell suspensions as a response to salvimulticanol treatment in a dose-dependent manner (IC50: 25.1 ± 1.2 µM) as compared to the methyl ester of candesalvone B which exerted a weaker inhibition (IC50: 69.2 ± 3.0 µM). This decline in NO percentage was comparable with a down-regulation of iNOS expression by western blotting. Salvimulticanol strongly interacted with both the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD-2) complex and the inhibitor of nuclear factor kappa-B (NF-κB) kinase subunit beta (IKKß) to disrupt their inflammatory activation due to the significant hydrogen bonds and effective interactions with amino acid residues present in the target proteins' active sites. S.multicaulis is a rich natural source of the aromatic abietane diterpenoid, salvimulticanol, which exerted a strong anti-inflammatory effect through targeting iNOS and diminishing NO production in LPS-induced RAW264.7 cells in a mechanism that is dependent on the inhibition of TLR4-MD-2 and IKKß as activators of the classical NF-κB-mediated inflammatory pathway.