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1.
Carbohydr Polym ; 338: 122199, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38763725

RESUMO

Deep eutectic solvents (DES) emerge as promising alternatives to conventional solvents, offering outstanding extraction capabilities, low toxicity, eco-friendliness, straightforward synthesis procedures, broad applicability, and impressive recyclability. DES are synthesized by combining two or more components through various synthesis procedures, such as heat-assisted mixing/stirring, grinding, freeze drying, and evaporation. Polysaccharides, as abundant natural materials, are highly valued for their biocompatibility, biodegradability, and sustainability. These versatile biopolymers can be derived from various natural sources such as plants, algae, animals, or microorganisms using diverse extraction techniques. This review explores the synthesis procedures of DES, their physicochemical properties, characterization analysis, and their application in polysaccharide extraction. The extraction optimization strategies, parameters affecting DES-based polysaccharide extraction, and separation mechanisms are comprehensively discussed. Additionally, this review provides insights into recently developed molecular guides for DES screening and the utilization of artificial neural networks for optimizing DES-based extraction processes. DES serve as excellent extraction media for polysaccharides from different sources, preserving their functional features. They are utilized both as extraction solvents and as supporting media to enhance the extraction abilities of other solvents. Continued research aims to improve DES-based extraction methods and achieve selective, energy-efficient processes to meet the demands of this expanding field.


Assuntos
Solventes Eutéticos Profundos , Polissacarídeos , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Solventes Eutéticos Profundos/química , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Animais , Solventes/química , Fracionamento Químico/métodos , Plantas/química
2.
J Sep Sci ; 47(9-10): e2300898, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38726747

RESUMO

Based on the specific binding of drug molecules to cell membrane receptors, a screening and separation method for active compounds of natural products was established by combining phospholipase C (PLC) sensitized hollow fiber microscreening by a solvent seal with high-performance liquid chromatography technology. In the process, the factors affecting the screening were optimized. Under the optimal screening conditions, we screened honokiol (HK), magnolol (MG), negative control drug carbamazepine, and positive control drug amentoflavone, the repeatability of the method was tested. The PLC activity was determined before and after the screening. Experimental results showed that the sensitization factors of PLC of HK and MG were 61.0 and 48.5, respectively, and amentoflavone was 15.0, carbamazepine could not bind to PLC. Moreover, the molecular docking results were consistent with this measurement, indicating that HK and MG could be combined with PLC, and they were potential interacting components with PLC. This method used organic solvent to seal the PLC greatly ensuring the activity, so this method had the advantage of integrating separation, and purification with screening, it not only exhibited good reproducibility and high sensitivity but was also suitable for screening the active components in natural products by various targets in vitro.


Assuntos
Produtos Biológicos , Fosfolipases Tipo C , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Produtos Biológicos/isolamento & purificação , Fosfolipases Tipo C/metabolismo , Fosfolipases Tipo C/química , Fosfolipases Tipo C/antagonistas & inibidores , Cromatografia Líquida de Alta Pressão , Simulação de Acoplamento Molecular , Lignanas/química , Lignanas/isolamento & purificação , Lignanas/farmacologia , Compostos de Bifenilo/antagonistas & inibidores , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/isolamento & purificação , Humanos , Compostos Alílicos , Fenóis
3.
Molecules ; 29(9)2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38731531

RESUMO

Actinomycetes have long been recognized as an important source of antibacterial natural products. In recent years, actinomycetes in extreme environments have become one of the main research directions. Streptomyces sp. KN37 was isolated from the cold region of Kanas in Xinjiang. It demonstrated potent antimicrobial activity, but the primary active compounds remained unclear. Therefore, we aimed to combine genomics with traditional isolation methods to obtain bioactive compounds from the strain KN37. Whole-genome sequencing and KEGG enrichment analysis indicated that KN37 possesses the potential for synthesizing secondary metabolites, and 41 biosynthetic gene clusters were predicted, some of which showed high similarity to known gene clusters responsible for the biosynthesis of antimicrobial antibiotics. The traditional isolation methods and activity-guided fractionation were employed to isolate and purify seven compounds with strong bioactivity from the fermentation broth of the strain KN37. These compounds were identified as 4-(Diethylamino)salicylaldehyde (1), 4-Nitrosodiphenylamine (2), N-(2,4-Dimethylphenyl)formamide (3), 4-Nitrocatechol (4), Methylsuccinic acid (5), Phenyllactic acid (6) and 5,6-Dimethylbenzimidazole (7). Moreover, 4-(Diethylamino)salicylaldehyde exhibited the most potent inhibitory effect against Rhizoctonia solani, with an EC50 value of 14.487 mg/L, while 4-Nitrosodiphenylamine showed great antibacterial activity against Erwinia amylovora, with an EC50 value of 5.715 mg/L. This study successfully isolated several highly active antimicrobial compounds from the metabolites of the strain KN37, which could contribute as scaffolds for subsequent chemical synthesis. On the other hand, the newly predicted antibiotic-like substances have not yet been isolated, but they still hold significant research value. They are instructive in the study of active natural product biosynthetic pathways, activation of silent gene clusters, and engineering bacteria construction.


Assuntos
Genômica , Família Multigênica , Streptomyces , Streptomyces/genética , Streptomyces/metabolismo , Streptomyces/química , Genômica/métodos , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/biossíntese , Testes de Sensibilidade Microbiana , Produtos Biológicos/farmacologia , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Agricultura/métodos , Sequenciamento Completo do Genoma
4.
Mar Drugs ; 22(4)2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38667798

RESUMO

Three pairs of enantiomers (1-3)-the new 12R-aloesol (1a) and two new fatty acids (2 and 3)-and one new natural product (4) together three known compounds (5-7) were isolated from a coral-reef-derived Streptomyces sp. SCSIO 66814. Their structures were determined through extensive spectroscopic analysis, chiral analysis, and single-crystal X-ray diffraction data. Compounds 2 and 3 were presumed to be intermediates for further generating homononactic acid (5) and nonactic acid, and the latter two molecules were able to act as precursors to form macrotetrolides with remarkable biological activity. The isolation of related precursors, compounds 2-5, provided more evidence to support the proposal of a plausible biosynthetic pathway for nonactic acid and its homologs. Additionally, (+)-1 exhibited a weak activity against DPPH radicals.


Assuntos
Antozoários , Cromonas , Streptomyces , Streptomyces/metabolismo , Streptomyces/química , Cromonas/química , Cromonas/isolamento & purificação , Cromonas/farmacologia , Estereoisomerismo , Antozoários/química , Animais , Cristalografia por Raios X , Ácidos Graxos/química , Ácidos Graxos/isolamento & purificação , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Produtos Biológicos/isolamento & purificação , Estrutura Molecular
5.
Mar Drugs ; 22(4)2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38667799

RESUMO

Techniques for extracting important bioactive molecules from seafood byproducts, viz., bones, heads, skin, frames, fins, shells, guts, and viscera, are receiving emphasis due to the need for better valorization. Employing green extraction technologies for efficient and quality production of these bioactive molecules is also strictly required. Hence, understanding the extraction process parameters to effectively design an applicable optimization strategy could enable these improvements. In this review, statistical optimization strategies applied for the extraction process parameters of obtaining bioactive molecules from seafood byproducts are focused upon. The type of experimental designs and techniques applied to criticize and validate the effects of independent variables on the extraction output are addressed. Dominant parameters studied were the enzyme/substrate ratio, pH, time, temperature, and power of extraction instruments. The yield of bioactive compounds, including long-chain polyunsaturated fatty acids, amino acids, peptides, enzymes, gelatine, collagen, chitin, vitamins, polyphenolic constituents, carotenoids, etc., were the most studied responses. Efficiency and/or economic and quality considerations and their selected optimization strategies that favor the production of potential bioactive molecules were also reviewed.


Assuntos
Alimentos Marinhos , Animais , Organismos Aquáticos , Humanos , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação
6.
Bioorg Chem ; 147: 107389, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38677011

RESUMO

The leaves of Odontonema strictum, a tropical plant used for its antihypertensive properties, are rich in nutrients and biologically active phytochemicals, such as ß-sitosterol, stigmasterol, umuravumbolide, deacetylumuravumbolide, dideacetylboronolide, deacetylboronolide, verbascoside, and isoverbascoside. In addition, its roots are rich in ß-sitosterol, stigmasterol, and the iridoid glycoside ß-O-methyl-unedoside. Ingestion of the roots was reported to have a sedative effect in a dog was previously reported on a dog eating the roots of this plant. In the present study, we report for the first time the cell proliferation- and neurite outgrowth-promoting effects in PC12 neuronal cells of the isolated organic compounds and crude extracts from O. strictum. Pituitary adenylate cyclase-activating peptide (PACAP) and quercetin were used as positive controls. At the concentration of 0.2 µg/mL, ß-sitosterol was more potent than quercetin and displayed the same activity (>45 µm/cell) as PACAP (100 nM). At a low concentration (0.04 µg/mL), verbascoside and isoverbascoside showed the strongest neurite outgrowth-promoting effect (neurite length of 30 to 35 µm/cell). Our results indicate that phytomedicines made from O. strictum may be useful in preventing neurodegenerative diseases.


Assuntos
Produtos Biológicos , Proliferação de Células , Crescimento Neuronal , Animais , Células PC12 , Crescimento Neuronal/efeitos dos fármacos , Ratos , Produtos Biológicos/farmacologia , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Estrutura Molecular , Relação Dose-Resposta a Droga , Relação Estrutura-Atividade , Neurônios/efeitos dos fármacos , Neurônios/citologia , Folhas de Planta/química
7.
J Chromatogr A ; 1716: 464643, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38232639

RESUMO

Peptidyl arginine deiminase 4 (PAD4) is an important biocatalytic enzymes involved in the conversion of protein arginine to citrulline, its dysregulation has a great impact on many physiological processes. Recently, PAD4 has emerged as a potential therapeutic target for the treatment of various diseases including rheumatoid arthritis (RA). Traditional Chinese Medicines (TCMs), also known as herbal plants, have gained great attention by the scientific community due to their good therapeutic performance and far fewer side effects observed in the clinical treatment. However, limited researches have been reported to screen natural PAD4 inhibitors from herbal plants. The color developing reagent (COLDER) or fluorescence based methods have been widely used in PAD4 activity assay and inhibitor screening. However, both methods measure the overall absorbance or fluorescence in the reaction solution, which are easy to be affected by the background interference due to colorful extracts from herbal plants. In this study, a simple, and robust high-performance liquid chromatography ultraviolet-visible (HPLC-UV) based method was developed to determine PAD4 activity. The proposed strategy was established based on COLDER principle, while used hydrophilic l-arginine instead of hydrophobic N-benzoyl-l-arginine ethyl ester (BAEE) as a new substrate to determine PAD4 inhibition activity of herbal extracts. The herbal extracts and PAD4 generated hydrophobic l-citrulline were successfully separated by the HPLC, and the developed method was optimized and validated with a known PAD4 inhibitor (GSK484) in comparison with COLDER assay. The IC50 value of GSK484 measured by HPLC-UV method was 153 nM, and the detection limit of the citrulline was 0.5 nmol, respectively, with a linear range of 0.5 nmol to 20 nmol. The IC50 value of the HPLC-UV method was improved by nearly three times compared with COLDER assay (527 nM), and the results indicated the reliability of PAD4 inhibition via HPLC-UV method. The inhibitory effect against PAD4 were fast and accurately screened for the twenty-four extracts from eight herbs. Among them, Ephedra Herba extracts showed significant inhibitory activity against the PAD4 with the IC50 values of three extracts (ethanol, ethyl acetate and water) ranging from 29.11 µg/mL to 41.36 µg/mL, which may help researchers to discover novel natural compounds holding high PAD4 inhibition activity.


Assuntos
Produtos Biológicos , Medicamentos de Ervas Chinesas , Inibidores Enzimáticos , Proteína-Arginina Desiminase do Tipo 4 , Cromatografia Líquida de Alta Pressão , Citrulina , Proteína-Arginina Desiminase do Tipo 4/antagonistas & inibidores , Reprodutibilidade dos Testes , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/farmacologia , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/farmacologia , Medicamentos de Ervas Chinesas/química
8.
Chem Pharm Bull (Tokyo) ; 71(10): 756-765, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37779077

RESUMO

In this review, our resent pharmaceutical food science research for bio-functional molecules obtained from natural resources that contribute to i) suppression of postprandial blood glucose elevation and/or improvement of glucose tolerance and ii) reduction of visceral fat accumulation and improvement of lipid metabolism were summarized. Based on studies using MONOTORI science, salacinol (1), neokotalanol (4), and trans-tiliroside (20) have been approved or notified by the Consumer Affairs Agency in Japan as functional substances in food with health claims, Food for Specified Health Use and Food with Functional Claims.


Assuntos
Produtos Biológicos , Glicemia , Tecnologia de Alimentos , Alimento Funcional , Hipoglicemiantes , Hipolipemiantes , Metabolismo dos Lipídeos , Tecnologia de Alimentos/tendências , Japão , Gordura Intra-Abdominal/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Glicemia/efeitos dos fármacos , Humanos , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/farmacologia , Hipolipemiantes/química , Hipolipemiantes/isolamento & purificação , Hipolipemiantes/farmacologia , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/farmacologia
9.
Molecules ; 28(15)2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37570750

RESUMO

Matrine is a quinoline alkaloid extracted and separated from the dried root, fruit, and other parts of the plant Sophora flavescens using an organic solvent. Matrine exhibits a variety of biological activities and is widely used in pharmacy, agronomy, and other fields. Due to its low bioavailability, poor chemical stability, and toxicity to the central nervous system, a large number of researchers have searched for matrine derivatives with higher biological activity and safety by modifying its structure. In this review article, the research progress of matrine derivatives obtained using two methods (extraction from Sophora flavescens and structural modifications) from 2018 to 2022 in terms of pharmacological activity, mechanism of action, and structure-activity relationship are presented. The modification of matrine over the past five years has been mainly on the D-ring. Many new matrine alkaloids have been extracted from natural products, some of which have good pharmacological activity, which broadens the strategy for matrine structural modification in the future.


Assuntos
Produtos Biológicos , Matrinas , Sophora flavescens , Matrinas/síntese química , Matrinas/química , Matrinas/isolamento & purificação , Matrinas/farmacologia , Produtos Biológicos/síntese química , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/farmacologia , Sophora flavescens/química , Raízes de Plantas/química , Frutas/química , Relação Estrutura-Atividade , Humanos , Animais , Linhagem Celular
10.
Org Lett ; 24(40): 7328-7333, 2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36200745

RESUMO

Molecular network analysis of Streptomyces sp. CMB-MW079 detected rare phosphorylated natural products. Miniaturized cultivation profiling (MATRIX) established optimal conditions for the production, isolation, and identification of the polyketide δ-lactone phoslactomycin E (1) and new ester homologues, phoslactomycins J and K (2 and 3), as well as unprecedented heterocyclic analogues, the tetrahydrofuran cyclolactomycins A-D (4-7) and γ-lactone isocyclolactomycins A-C (8-10). We propose a biogenetic relationship linking these cometabolites with the known lactomycins A-C which were tentatively identified as minor cometabolites.


Assuntos
Produtos Biológicos , Lactonas , Compostos Organofosforados , Policetídeos , Streptomyces , Vespas , Animais , Austrália , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/farmacologia , Linhagem Celular Tumoral , Ésteres/química , Furanos/química , Humanos , Lactonas/química , Lactonas/isolamento & purificação , Lactonas/farmacologia , Estrutura Molecular , Compostos Organofosforados/química , Compostos Organofosforados/isolamento & purificação , Compostos Organofosforados/farmacologia , Policetídeos/química , Policetídeos/isolamento & purificação , Policetídeos/farmacologia , Streptomyces/química , Streptomyces/metabolismo , Vespas/microbiologia
11.
J Nat Prod ; 85(9): 2127-2134, 2022 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-36044031

RESUMO

Cyclotides are mini-proteins with potent bioactivities and outstanding potential for agricultural and pharmaceutical applications. More than 450 different plant cyclotides have been isolated from six angiosperm families. In Brazil, studies involving this class of natural products are still scarce, despite its rich floristic diversity. Herein were investigated the cyclotides from Anchietea pyrifolia roots, a South American medicinal plant from the family Violaceae. Fourteen putative cyclotides were annotated by LC-MS. Among these, three new bracelet cyclotides, anpy A-C, and the known cycloviolacins O4 (cyO4) and O17 (cyO17) were sequenced through a combination of chemical and enzymatic reactions followed by MALDI-MS/MS analysis. Their cytotoxic activity was evaluated by a cytotoxicity assay against three human cancer cell lines (colorectal carcinoma cells: HCT 116 and HCT 116 TP53-/- and breast adenocarcinoma, MCF 7). For all assays, the IC50 values of isolated compounds ranged between 0.8 and 7.3 µM. CyO17 was the most potent cyclotide for the colorectal cancer cell lines (IC50, 0.8 and 1.2 µM). Furthermore, the hemolytic activity of anpy A and B, cyO4, and cyO17 was assessed, and the cycloviolacins were the least hemolytic (HD50 > 156 µM). This work sheds light on the cytotoxic effects of the anpy cyclotides against cancer cells. Moreover, this study expands the number of cyclotides obtained to date from Brazilian plant biodiversity and adds one more genus containing these molecules to the list of the Violaceae family.


Assuntos
Produtos Biológicos , Ciclotídeos , Proteínas de Plantas , Violaceae , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/farmacologia , Brasil , Linhagem Celular Tumoral , Ciclotídeos/química , Ciclotídeos/isolamento & purificação , Ciclotídeos/farmacologia , Humanos , Proteínas de Plantas/química , Proteínas de Plantas/isolamento & purificação , Proteínas de Plantas/farmacologia , Espectrometria de Massas em Tandem , Violaceae/química
12.
J Biol Chem ; 298(9): 102300, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35931117

RESUMO

Natural products constitute and significantly impact many current anti-cancer medical interventions. A subset of natural products induces injury processes in malignant cells that recruit and activate host immune cells to produce an adaptive anti-cancer immune response, a process known as immunogenic cell death. However, a challenge in the field is to delineate forms of cell death and injury that best promote durable antitumor immunity. Addressing this with a single-cell chemical biology natural product discovery platform, like multiplex activity metabolomics, would be especially valuable in human leukemia, where cancer cells are heterogeneous and may react differently to the same compounds. Herein, a new ten-color, fluorescent cell barcoding-compatible module measuring six immunogenic cell injury signaling readouts are as follows: DNA damage response (γH2AX), apoptosis (cCAS3), necroptosis (p-MLKL), mitosis (p-Histone H3), autophagy (LC3), and the unfolded protein response (p-EIF2α). A proof-of-concept screen was performed to validate functional changes in single cells induced by secondary metabolites with known mechanisms within bacterial extracts. This assay was then applied in multiplexed activity metabolomics to reveal an unexpected mammalian cell injury profile induced by the natural product narbomycin. Finally, the functional consequences of injury pathways on immunogenicity were compared with three canonical assays for immunogenic hallmarks, ATP, HMGB1, and calreticulin, to correlate secondary metabolite-induced cell injury profiles with canonical markers of immunogenic cell death. In total, this work demonstrated a new phenotypic screen for discovery of natural products that modulate injury response pathways that can contribute to cancer immunogenicity.


Assuntos
Antineoplásicos , Produtos Biológicos , Proteína HMGB1 , Metabolômica , Neoplasias , Análise de Célula Única , Trifosfato de Adenosina , Animais , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/farmacologia , Biomarcadores , Calreticulina/metabolismo , Morte Celular/imunologia , Proteína HMGB1/metabolismo , Histonas/metabolismo , Humanos , Metabolômica/métodos , Neoplasias/imunologia
13.
Mar Drugs ; 20(3)2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35323477

RESUMO

One new depsidone derivative, aspergillusidone H (3), along with seven known biosynthetically related chlorinated polyketides, were obtained from the Beibu Gulf coral-derived fungus Aspergillus unguis GXIMD 02505. Their structures were determined by comprehensive physicochemical and spectroscopic data interpretation. Notably, the X-ray crystal structure of 2 and the previously unknown absolute configuration of 8, assigned by ECD calculations, are described here for the first time. Compounds 1-5, 7 and 8 exhibited inhibition of lipopolysaccharide (LPS)-induced NF-κB in RAW 264.7 macrophages at 20 µM. In addition, the two potent inhibitors (2 and 7) dose-dependently suppressed RANKL-induced osteoclast differentiation without any evidence of cytotoxicity in bone marrow macrophages cells (BMMs). This is the first report of osteoclastogenesis inhibitory activity for the metabolites of these kinds. Besides, compounds 1, 2, 4, and 6-8 showed inhibitory activity against marine biofilm-forming bacteria, methicillin-resistant Staphylococcus aureus, Microbulbifer variabilis, Marinobacterium jannaschii, and Vibrio pelagius, with their MIC values ranging from 2 to 64 µg/mL. These findings provide a basis for further development of chlorinated polyketides as potential inhibitors of osteoclast differentiation and/or for use as anti-fouling agents.


Assuntos
Antozoários/microbiologia , Antibacterianos , Aspergillus/química , Produtos Biológicos , Osteogênese/efeitos dos fármacos , Policetídeos , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/farmacologia , Células Cultivadas , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Camundongos , Estrutura Molecular , NF-kappa B/metabolismo , Oceanos e Mares , Policetídeos/química , Policetídeos/isolamento & purificação , Policetídeos/farmacologia , Ligante RANK
14.
Mar Drugs ; 20(3)2022 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-35323485

RESUMO

The biological screening of 44 marine sponge extracts for the research of bioactive molecules, with potential application in the treatment of age-related diseases (cancer and Alzheimer's disease) and skin aging, resulted in the selection of Scopalina hapalia extract for chemical study. As no reports of secondary metabolites of S. hapalia were found in the literature, we undertook this research to further extend current knowledge of Scopalina chemistry. The investigation of this species led to the discovery of four new compounds: two butenolides sinularone J (1) and sinularone K (2), one phospholipid 1-O-octadecyl-2-pentanoyl-sn-glycero-3-phosphocholine (3) and one lysophospholipid 1-O-(3-methoxy-tetradecanoyl)-sn-glycero-3-phosphocholine (4) alongside with known lysophospholipids (5 and 6), alkylglycerols (7-10), epidioxysterols (11 and 12) and diketopiperazines (13 and 14). The structure elucidation of the new metabolites (1-4) was determined by detailed spectroscopic analysis, including 1D and 2D NMR as well as mass spectrometry. Molecular networking was also explored to complement classical investigation and unravel the chemical classes within this species. GNPS analysis provided further information on potential metabolites with additional bioactive natural compounds predicted.


Assuntos
4-Butirolactona/análogos & derivados , Produtos Biológicos , Fosfolipídeos , Piperazinas , Poríferos/química , 4-Butirolactona/química , 4-Butirolactona/isolamento & purificação , Animais , Baías , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Comores , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Fosfolipídeos/química , Fosfolipídeos/isolamento & purificação , Piperazinas/química , Piperazinas/isolamento & purificação , Poríferos/metabolismo
15.
Mar Drugs ; 20(3)2022 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-35323489

RESUMO

Species misidentification in the field of natural products is an acknowledged problem. These errors are especially widespread in sponge studies, albeit rarely assessed and documented. As a case study, we aim to revisit reports of isomalabaricane triterpenes, isolated from four demosponge genera: Jaspis, Geodia, Stelletta and Rhabdastrella. From a total of 44 articles (1981-2022), 27 unique vouchers were listed, 21 of which were accessed and re-examined here: 11 (52.4%) of these were misidentified. Overall, 65.9% of the studies published an incorrect species name: previously identified Jaspis and Stelletta species were all in fact Rhabdastrella globostellata. We conclude that isomalabaricane triterpenes were isolated from only two Rhabdastrella species and possibly one Geodia species. In addition to shedding a new light on the distribution of isomalabaricane triterpenes, this study is an opportunity to highlight the crucial importance of vouchers in natural product studies. Doing so, we discuss the impact of species misidentification and poor accessibility of vouchers in the field of sponge natural products. We advocate for stricter voucher guidelines in natural product journals and propose a common protocol of good practice, in the hope of reducing misidentifications in sponge studies, ensure reproducibility of studies, and facilitate follow-up work on the original material.


Assuntos
Produtos Biológicos , Poríferos , Triterpenos , Animais , Produtos Biológicos/classificação , Produtos Biológicos/isolamento & purificação , Poríferos/química , Poríferos/classificação , Reprodutibilidade dos Testes , Triterpenos/classificação , Triterpenos/isolamento & purificação
16.
Mar Drugs ; 20(3)2022 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-35323511

RESUMO

Five undescribed butenolides including two pairs of enantiomers, (+)-asperteretal G (1a), (-)-asperteretal G (1b), (+)-asperteretal H (2a), (-)-asperteretal H (2b), asperteretal I (3), and para-hydroxybenzaldehyde derivative, (S)-3-(2,3-dihydroxy-3-methylbutyl)-4-hydroxybenzaldehyde (14), were isolated together with ten previously reported butenolides 4-13, from the coral-derived fungus Aspergillus terreus SCSIO41404. Enantiomers 1a/1b and 2a/2b were successfully purified by high performance liquid chromatography (HPLC) using a chiral column, and the enantiomers 1a and 1b were new natural products. Structures of the unreported compounds, including the absolute configurations, were elucidated by NMR and MS data, optical rotation, experimental and calculated electronic circular dichroism, induced circular dichroism, and X-ray crystal data. The isolated butenolides were evaluated for antibacterial, cytotoxic, and enzyme inhibitory activities. Compounds 7 and 12 displayed weak antibacterial activity, against Enterococcus faecalis (IC50 = 25 µg/mL) and Klebsiella pneumoniae (IC50 = 50 µg/mL), respectively, whereas 6 showed weak inhibitory effect on acetylcholinesterase. Nevertheless, most of the butenolides showed inhibition against pancreatic lipase (PL) with an inhibition rate of 21.2-73.0% at a concentration of 50 µg/mL.


Assuntos
4-Butirolactona/análogos & derivados , Antozoários/microbiologia , Antibacterianos , Aspergillus/química , Produtos Biológicos , Inibidores da Colinesterase , Lipase/antagonistas & inibidores , 4-Butirolactona/química , 4-Butirolactona/isolamento & purificação , 4-Butirolactona/farmacologia , Acetilcolinesterase/metabolismo , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Antibacterianos/toxicidade , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/farmacologia , Inibidores da Colinesterase/química , Inibidores da Colinesterase/isolamento & purificação , Inibidores da Colinesterase/farmacologia , Estrutura Molecular , Estereoisomerismo
17.
Mar Drugs ; 20(3)2022 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-35323513

RESUMO

Two new cyclized thiolopyrrolone derivatives, namely, thiolopyrrolone A (1) and 2,2-dioxidothiolutin (2), together with the kn own compound, thiolutin (3) were identified from a marine-derived Streptomyces sp. BTBU20218885, which was isolated from a mud sample collected from the coastal region of Xiamen, China. Their chemical structures were determined using spectroscopic data, including HRESIMS, 1D and 2D NMR techniques. 1 possessed a unique unsymmetrical sulfur-containing thiolopyrrolone structure. All the compounds were tested for bioactivities against Staphylococcus aureus, Escherichia coli, Bacille Calmette-Guérin (BCG), Mycobacterium tuberculosis, and Candida albicans. 1 displayed antibacterial activities against BCG, M. tuberculosis, and S. aureus with minimum inhibitory concentration (MIC) values of 10, 10, and 100 µg/mL, respectively. Thiolutin (3) showed antibacterial activities against E. coli, BCG, M. tuberculosis, and S. aureus with MIC values of 6.25, 0.3125, 0.625, and 3.125 µg/mL, respectively.


Assuntos
Anti-Infecciosos , Organismos Aquáticos/química , Produtos Biológicos , Pirróis , Streptomyces/química , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Organismos Aquáticos/genética , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/farmacologia , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Ciclização , Testes de Sensibilidade Microbiana , Pirróis/química , Pirróis/isolamento & purificação , Pirróis/farmacologia , Streptomyces/genética
18.
Mar Drugs ; 20(3)2022 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-35323515

RESUMO

Aspergillus is well-known as the second-largest contributor of fungal natural products. Based on NMR guided isolation, three nitrogen-containing secondary metabolites, including two new compounds, variotin B (1) and coniosulfide E (2), together with a known compound, unguisin A (3), were isolated from the ethyl acetate (EtOAc) extract of the deep-sea fungus Aspergillus unguis IV17-109. The planar structures of 1 and 2 were elucidated by an extensive analysis of their spectroscopic data (HRESIMS, 1D and 2D NMR). The absolute configuration of 2 was determined by comparison of its optical rotation value with those of the synthesized analogs. Compound 2 is a rare, naturally occurring substance with an unusual cysteinol moiety. Furthermore, 1 showed moderate anti-inflammatory activity with an IC50 value of 20.0 µM. These results revealed that Aspergillus unguis could produce structurally diverse nitrogenous secondary metabolites, which can be used for further studies to find anti-inflammatory leads.


Assuntos
Anti-Inflamatórios , Aspergillus/química , Produtos Biológicos , Peptídeos Cíclicos , Sulfetos , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/metabolismo , Organismos Aquáticos , Aspergillus/metabolismo , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Nitrogênio/química , Peptídeos Cíclicos/química , Peptídeos Cíclicos/isolamento & purificação , Peptídeos Cíclicos/metabolismo , Pirrolidinonas/química , Pirrolidinonas/isolamento & purificação , Pirrolidinonas/metabolismo , Células RAW 264.7 , Metabolismo Secundário , Sulfetos/química , Sulfetos/isolamento & purificação , Sulfetos/metabolismo
19.
Mar Drugs ; 20(3)2022 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-35323514

RESUMO

The world is already facing the devastating effects of the SARS-CoV-2 pandemic. A disseminated mucormycosis epidemic emerged to worsen this situation, causing havoc, especially in India. This research aimed to perform a multitargeted docking study of marine-sponge-origin bioactive compounds against mucormycosis. Information on proven drug targets and marine sponge compounds was obtained via a literature search. A total of seven different targets were selected. Thirty-five compounds were chosen using the PASS online program. For homology modeling and molecular docking, FASTA sequences and 3D structures for protein targets were retrieved from NCBI and PDB databases. Autodock Vina in PyRx 0.8 was used for docking studies. Further, molecular dynamics simulations were performed using the IMODS server for top-ranked docked complexes. Moreover, the drug-like properties and toxicity analyses were performed using Lipinski parameters in Swiss-ADME, OSIRIS, ProTox-II, pkCSM, and StopTox servers. The results indicated that naamine D, latrunculin A and S, (+)-curcudiol, (+)-curcuphenol, aurantoside I, and hyrtimomine A had the highest binding affinity values of -8.8, -8.6, -9.8, -11.4, -8.0, -11.4, and -9.0 kcal/mol, respectively. In sum, all MNPs included in this study are good candidates against mucormycosis. (+)-curcudiol and (+)-curcuphenol are promising compounds due to their broad-spectrum target inhibition potential.


Assuntos
Antifúngicos , Produtos Biológicos , Tratamento Farmacológico da COVID-19 , Mucormicose/tratamento farmacológico , Poríferos/química , SARS-CoV-2 , Animais , Antifúngicos/química , Antifúngicos/isolamento & purificação , Antifúngicos/farmacocinética , Antifúngicos/toxicidade , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/farmacocinética , Produtos Biológicos/toxicidade , COVID-19/complicações , Coinfecção , Proteínas Fúngicas/química , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Mucormicose/etiologia , Testes de Toxicidade Aguda
20.
Mar Drugs ; 20(3)2022 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-35323517

RESUMO

Three complex polyoxygenated diterpenoids possessing uncommon tetradecahydro-2,13:6,9-diepoxybenzo[10]annulene scaffold, namely ximaoornatins A-C (1-3), one new eunicellin-type diterpene, litophynin K (4), and a related known compound, litophynol B (5) were isolated from the South China Sea soft coral Sinularia ornata. The structures and absolute configurations of 1-4 were established by extensive spectroscopic analysis, X-ray diffraction analysis, and/or modified Mosher's method. A plausible biosynthetic relationship of 1 and its potential precursor 4 was proposed. In a bioassay, none of the isolated compounds showed obvious anti-inflammatory activity on LPS-induced TNF-α release in RAW264.7 macrophages and PTP1B inhibitory effects.


Assuntos
Antozoários/química , Produtos Biológicos , Diterpenos , Animais , Antozoários/metabolismo , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/metabolismo , Diterpenos/química , Diterpenos/isolamento & purificação , Diterpenos/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , Modelos Moleculares , Estrutura Molecular , Proteína Tirosina Fosfatase não Receptora Tipo 1/química , Células RAW 264.7 , Fator de Necrose Tumoral alfa/metabolismo
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