RESUMEN
Anithiactin D (1), a 2-phenylthiazole class of natural products, was isolated from marine mudflat-derived actinomycetes Streptomyces sp. 10A085. The chemical structure of 1 was elucidated based on the interpretation of NMR and MS data. The absolute configuration of 1 was determined by comparing the experimental and calculated electronic circular dichroism (ECD) spectral data. Anithiactin D (1) significantly decreased cancer cell migration and invasion activities at a concentration of 5 µM via downregulation of the epithelial-to-mesenchymal transition (EMT) markers in A549, AGS, and Caco-2 cell lines. Moreover, 1 inhibited the activity of Rho GTPases, including Rac1 and RhoA in the A549 cell line, suppressed RhoA in AGS and Caco-2 cell lines, and decreased the mRNA expression levels of some matrix metalloproteinases (MMPs) in AGS and Caco-2 cell lines. Thus 1, which is a new entity of the 2-phenylthiazole class of natural products with a unique aniline-indole fused moiety, is a potent inhibitor of the motility of cancer cells.
Asunto(s)
Neoplasias , Streptomyces , Humanos , Línea Celular Tumoral , Células CACO-2 , Streptomyces/metabolismo , Células A549 , Proteínas de Unión al GTP rho/metabolismo , Movimiento Celular , Transición Epitelial-MesenquimalRESUMEN
The pathogenic consequences of 369 unique human HsMLH1 missense variants has been hampered by the lack of a detailed function in mismatch repair (MMR). Here single-molecule images show that HsMSH2-HsMSH6 provides a platform for HsMLH1-HsPMS2 to form a stable sliding clamp on mismatched DNA. The mechanics of sliding clamp progression solves a significant operational puzzle in MMR and provides explicit predictions for the distribution of clinically relevant HsMLH1 missense mutations.
Asunto(s)
Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Reparación de la Incompatibilidad de ADN , Proteínas de Unión al ADN/genética , ADN/genética , Homólogo 1 de la Proteína MutL/genética , Proteína 2 Homóloga a MutS/genética , Mutación Missense , Sitios de Unión , Neoplasias Colorrectales Hereditarias sin Poliposis/metabolismo , Neoplasias Colorrectales Hereditarias sin Poliposis/patología , ADN/química , ADN/metabolismo , Daño del ADN , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/metabolismo , Humanos , Modelos Moleculares , Homólogo 1 de la Proteína MutL/química , Homólogo 1 de la Proteína MutL/metabolismo , Proteína 2 Homóloga a MutS/química , Proteína 2 Homóloga a MutS/metabolismo , Unión Proteica , Conformación Proteica en Hélice alfa , Conformación Proteica en Lámina beta , Dominios y Motivos de Interacción de ProteínasRESUMEN
Marinobazzanan (1), a new bazzanane-type sesquiterpenoid, was isolated from a marine-derived fungus belonging to the genus Acremonium. The chemical structure of 1 was elucidated using NMR and mass spectroscopic data, while the relative configurations were established through the analysis of NOESY data. The absolute configurations of 1 were determined by the modified Mosher's method as well as vibrational circular dichroism (VCD) spectra calculation and it was determined as 6R, 7R, 9R, and 10R. It was found that compound 1 was not cytotoxic to human cancer cells, including A549 (lung cancer), AGS (gastric cancer), and Caco-2 (colorectal cancer) below the concentration of 25 µM. However, compound 1 was shown to significantly decrease cancer-cell migration and invasion and soft-agar colony-formation ability at concentrations ranging from 1 to 5 µM by downregulating the expression level of KITENIN and upregulating the expression level of KAI1. Compound 1 suppressed ß-catenin-mediated TOPFLASH activity and its downstream targets in AGS, A549, and Caco-2 and slightly suppressed the Notch signal pathway in three cancer cells. Furthermore, 1 also reduced the number of metastatic nodules in an intraperitoneal xenograft mouse model.
Asunto(s)
Antineoplásicos , Sesquiterpenos , Humanos , Animales , Ratones , Células CACO-2 , Transformación Celular Neoplásica , Antineoplásicos/química , Movimiento Celular , Sesquiterpenos/farmacología , Sesquiterpenos/química , Estructura MolecularRESUMEN
Ipomoea pes-caprae (Linn.) R. Br. (Convolvulaceae) is a halophytic plant that favorably grows in tropical and subtropical countries in Asia, America, Africa, and Australia. Even though this plant is considered a pan-tropical plant, I. pes-caprae has been found to occur in inland habitats and coasts of wider areas, such as Spain, Anguilla, South Africa, and Marshall Island, either through a purposeful introduction, accidentally by dispersal, or by spreading due to climate change. The plant parts are used in traditional medicine for treating a wide range of diseases, such as inflammation, gastrointestinal disorders, pain, and hypertension. Previous phytochemical analyses of the plant have revealed pharmacologically active components, such as alkaloids, glycosides, steroids, terpenoids, and flavonoids. These phytoconstituents are responsible for the wide range of biological activities possessed by I. pes-caprae plant parts and extracts. This review arranges the previous reports on the botany, distribution, traditional uses, chemical constituents, and biological activities of I. pes-caprae to facilitate further studies that would lead to the discovery of novel bioactive natural products from this halophyte.
Asunto(s)
Botánica , Ipomoea , Medicina Tradicional , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Plantas Tolerantes a la SalRESUMEN
Acremonamide (1) was isolated from a marine-derived fungus belonging to the genus Acremonium. The chemical structure of 1 was established using MS, UV, and NMR spectroscopic data analyses. Acremonamide (1) was found to contain N-Me-Phe, N-Me-Ala, Val, Phe, and 2-hydroxyisovaleric acid. The absolute configurations of the four aforementioned amino acids were determined through acid hydrolysis followed by the advanced Marfey's method, whereas the absolute configuration of 2-hydroxyisovaleric acid was determined through GC-MS analysis after formation of the O-pentafluoropropionylated derivative of the (-)-menthyl ester of 2-hydroxyisovaleric acid. As an intrinsic biological activity, acremonamide (1) did not exert cytotoxicity to cancer and noncancer cells and increased the migration and invasion. Based on these activities, the wound healing properties of acremonamide (1) were confirmed in vitro and in vivo.
Asunto(s)
Acremonium/química , Péptidos Cíclicos/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Organismos Acuáticos/química , Células CACO-2 , Células HaCaT , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Estructura Molecular , Células 3T3 NIH , Péptidos Cíclicos/aislamiento & purificaciónRESUMEN
Four new chlorinated meroterpenoids, merochlorins G-J (1-4), and 10, a dihydronaphthalenedione precursor, along with known merochlorins A (5) and C-F (6-9), were obtained from cultivation of the bacterium strain Streptomyces sp. CNH-189, which was isolated from marine sediment. The planar structures of compounds 1-4 and 10 were elucidated by interpretation of MS, UV, and NMR spectroscopic data. The relative configurations of compounds 1-4 were determined via analysis of nuclear Overhauser effect (NOE) spectroscopic data, after which their absolute configurations were established by comparing the experimental electronic circular dichroism (ECD) spectra of compounds 1-4 to those of previously reported possible enantiomer models and DP4 calculations. Compound 3 displayed strong antibacterial activities against Bacillus subtilis, Kocuria rhizophila, and Staphylococcus aureus, with MIC values of 1, 2, and 2 µg/mL, respectively, whereas compound 1 exhibited weak antibacterial effects on these three strains, with a 16-32 µg/mL MIC value range.
Asunto(s)
Antibacterianos/farmacología , Streptomyces , Terpenos/farmacología , Animales , Antibacterianos/química , Organismos Acuáticos , Bacillus subtilis/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Micrococcaceae/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Terpenos/químicaRESUMEN
Five new bicyclic carboxylic acids were obtained by antibacterial activity-guided isolation from a Korean colonial tunicate Didemnum sp. Their structures were elucidated by the interpretation of NMR, MS and CD spectroscopic data. They all belong to the class of aplidic acids. Three of them were amide derivatives (1-3), and the other two were dicarboxylic derivatives (4 and 5). The absolute configurations were determined by a bisignate pattern of CD spectroscopy, which revealed that the absolute configurations of amides were opposite to those of dicarboxylates at every stereogenic centers. Compound 2 exhibited the most potent antibacterial activity (MIC, 2 µg/mL).
Asunto(s)
Antibacterianos/química , Antibacterianos/farmacología , Ácidos Grasos/química , Ácidos Grasos/farmacología , Urocordados/química , Animales , Estructura Molecular , Staphylococcus aureus/efectos de los fármacosRESUMEN
Salicornia europaea L. is a halophyte that grows in salt marshes and muddy seashores, which is widely used both as traditional medicine and as an edible vegetable. This salt-tolerant plant is a source of diverse secondary metabolites with several therapeutic properties, including antioxidant, antidiabetic, cytotoxic, anti-inflammatory, and anti-obesity effects. Therefore, this review summarizes the chemical structure and biological activities of secondary metabolites isolated from Salicornia europaea L.
Asunto(s)
Chenopodiaceae/química , Animales , Humanos , Fitoquímicos/química , Plantas Tolerantes a la Sal/químicaRESUMEN
Two new chlorinated secondary metabolites, saccharochlorines A and B (1 and 2), were isolated from the saline cultivation of a marine-derived bacterium Saccharomonospora sp. (KCTC-19160). The chemical structures of the saccharochlorines were elucidated by 2D NMR and MS spectroscopic data. Saccharochlorines A and B (1 and 2) exhibit weak inhibition of ß-secretase (BACE1) in biochemical inhibitory assay, but they induced the release of Aß (1-40) and Aß (1-42) in H4-APP neuroglial cells. This discrepancy might be derived from the differences between the cellular and sub-cellular environments or the epigenetic stimulation of BACE1 expression.
Asunto(s)
Acrilatos/química , Actinobacteria/química , Acrilatos/aislamiento & purificación , Acrilatos/metabolismo , Acrilatos/farmacología , Actinobacteria/metabolismo , Secretasas de la Proteína Precursora del Amiloide/antagonistas & inhibidores , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Péptidos beta-Amiloides/metabolismo , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Conformación Molecular , Neuroglía/citología , Neuroglía/efectos de los fármacos , Neuroglía/metabolismo , Fragmentos de Péptidos/metabolismoRESUMEN
Lycii Fructus is a traditional medicine used to prevent liver and kidney diseases, which commonly derives from Lycium chinense and Lycium barbarum. Here, the extracts and ethyl acetate-soluble fractions of L. chinense fruits exhibited better hepatoprotective effects than those of L. barbarum, which was likely due to differences in their composition. Therefore, GC-MS and HPLC analyses were conducted to characterize the metabolite differences between L. chinense and L. barbarum. Based on amino acid (AA) and phenolic acid (PA) profiling, 24 AAs and 9 PAs were identified in the two species. Moreover, each species exhibited unique and readily distinguishable AA and PA star graphic patterns. HPLC analysis elucidated composition differences between the ethyl acetate-soluble layers of the two compounds. Further, NMR analysis identified their chemical structures as 4-(2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl)butanoic acid and p-coumaric acid. The higher content of 4-(2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl)butanoic acid was detected in L. chinense, whereas the content of p-coumaric acid was higher in L. barbarum. Therefore, the differences in the relative contents of these two secondary metabolites in the ethyl acetate-soluble layer of Lycii Fructus could be a good marker to discriminate between L. chinense and L. barbarum.
Asunto(s)
Hepatocitos/efectos de los fármacos , Lycium/química , Lycium/clasificación , Extractos Vegetales/química , Extractos Vegetales/farmacología , Sustancias Protectoras/química , Sustancias Protectoras/farmacología , Aminoácidos , Supervivencia Celular/efectos de los fármacos , Fraccionamiento Químico , Relación Dosis-Respuesta a Droga , Cromatografía de Gases y Espectrometría de Masas , Células Hep G2 , Humanos , Hidroxibenzoatos , Estructura Molecular , Fitoquímicos/química , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Extractos Vegetales/análisis , Extractos Vegetales/aislamiento & purificación , Sustancias Protectoras/análisis , Sustancias Protectoras/aislamiento & purificaciónRESUMEN
CONTEXT: Research interest in monoamine oxidase (MAO) as a promising drug target for neurodegenerative diseases has a long history. However, efforts to develop MAO inhibitors (MAOIs) from marine sources have been limited, despite the increasing number of interesting marine natural products. OBJECTIVE: To review the potential of marine natural products as MAOIs source, including their activities and selectivity on MAO. METHODS: Public databases such as SciFinder, MarinLit and PubMed were systematically searched from 1991 until Dec 2019. MAO and MAOI were the key terms searched combined with marine natural products and marine. RESULTS: Six classes of marine natural products with good selectivity between the two MAO subtypes were organized with their selectivity and sources. CONCLUSIONS: This is the first review to investigate the potential of marine natural products as MAOIs source. Despite the small number of known MAOIs from marine sources, marine natural products are potential leads for the further development of MAOI drugs with novel chemical frames and good selectivity.
Asunto(s)
Productos Biológicos/aislamiento & purificación , Inhibidores de la Monoaminooxidasa/aislamiento & purificación , Enfermedades Neurodegenerativas/tratamiento farmacológico , Animales , Organismos Acuáticos , Productos Biológicos/farmacología , Desarrollo de Medicamentos , Humanos , Inhibidores de la Monoaminooxidasa/farmacología , Enfermedades Neurodegenerativas/fisiopatologíaRESUMEN
Photopiperazines A-D (1-4), unsaturated diketopiperazine derivatives, were isolated from the culture broth of a rare, marine-derived actinomycete bacterium, strain AJS-327. This strain shows very poor 16S rRNA sequence similarity to other members of the actinomycete family Streptomycetaceae, indicating it is likely a new lineage within this group. The structures of the photopiperazines were defined by analysis of HR-ESI-TOF-MS spectra in conjunction with the interpretation of 1D and 2D NMR data. The photopiperazines are sensitive to light, causing interconversion among the four olefin geometrical isomers, which made purification of each isomer challenging. The photopiperazines are highly cytotoxic metabolites that show selective toxicity toward U87 glioblastoma and SKOV3 ovarian cancer cell lines.
Asunto(s)
Actinobacteria/metabolismo , Neoplasias Encefálicas/metabolismo , Glioblastoma/metabolismo , Piperazinas/química , Streptomycetaceae/química , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Glioblastoma/patología , HumanosRESUMEN
Mycousfurans (1 and 2), two new usnic acid congeners, along with (-)-mycousnine (3), (-)-placodiolic acid (4), and (+)-usnic acid (5), were isolated using high-performance liquid chromatography-ultraviolet (HPLC-UV)-guided fractionation of extracts of Mycosphaerella sp. isolated from a marine sediment. The planar structures of 1 and 2 were elucidated using 1D and 2D NMR spectra. The relative configurations of the stereogenic carbons of 1 and 2 were established via analysis of their nuclear Overhauser spectroscopy (NOESY) spectra, and their absolute configurations were determined using a comparison of experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 1 and 2 were found to have antibacterial activity, showing moderate activity against Kocuria rhizophila and Staphylococcus aureus.
Asunto(s)
Antibacterianos/farmacología , Ascomicetos/química , Benzofuranos/farmacología , Furanos/farmacología , Sedimentos Geológicos/microbiología , Compuestos Heterocíclicos con 3 Anillos/farmacología , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Benzofuranos/química , Benzofuranos/aislamiento & purificación , Furanos/química , Furanos/aislamiento & purificación , Compuestos Heterocíclicos con 3 Anillos/química , Compuestos Heterocíclicos con 3 Anillos/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Micrococcaceae/efectos de los fármacos , Estructura Molecular , Staphylococcus aureus/efectos de los fármacosRESUMEN
A cytotoxic alkaloidal meroterpenoid, saccharoquinoline (1), has been isolated from the fermentation broth of the marine-derived bacterium Saccharomonospora sp. CNQ-490. The planar structure of 1 was elucidated by 1D, 2D NMR, and MS spectroscopic data analyzes, while the relative configuration of 1 was defined through the interpretation of NOE spectroscopic data. Saccharoquinoline (1) is composed of a drimane-type sesquiterpene unit in combination with an apparent 6,7,8-trihydroxyquinoline-2-carboxylic acid. This combination of biosynthetic pathways was observed for the first time in natural microbial products. Saccharoquinoline (1) was found to have cytotoxicity against the HCT-116 cancer cell line by inducing G1 arrest, which leads to cell growth inhibition.
Asunto(s)
Actinobacteria/metabolismo , Antineoplásicos/farmacología , Terpenos/química , Terpenos/farmacología , Actinobacteria/química , Antineoplásicos/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Modelos Moleculares , Estructura MolecularRESUMEN
Antartin (1), a new zizaane-type sesquiterpene, was isolated from Streptomyces sp. SCO736. The chemical structure of 1 was assigned from the interpretation of 1D and 2D NMR in addition to mass spectrometric data. The relative stereochemistry of 1 was determined by analysis of NOE data, while the absolute stereochemistry was decided based on a comparison of experimental and calculated electronic circular dichroism (ECD) spectra. Antartin (1) showed cytotoxicity against A549, H1299, and U87 cancer cell lines by causing cell cycle arrest at the G1 phase.
Asunto(s)
Citotoxinas/química , Sesquiterpenos/química , Streptomyces/química , Células A549 , Regiones Antárticas , Línea Celular Tumoral , Dicroismo Circular , Citotoxinas/farmacología , Fase G1/efectos de los fármacos , Sedimentos Geológicos/microbiología , Humanos , Espectroscopía de Resonancia Magnética/métodos , Sesquiterpenos/farmacologíaRESUMEN
Intensive study on the chemical components of a Korean marine sponge, Spongia sp., has led to the isolation of four new scalarane sesterterpenes, scalalactams Aâ»D (1â»4). Their chemical structures were elucidated from the analysis of spectroscopic data including 1D-and 2D-NMR as well as MS data. Scalalactams Aâ»D (1â»4) possess a scalarane carbon skeleton with a rare structural feature of a γ-lactam moiety within the molecules. Scalalactams A and B (1 and 2) have an extended isopropanyl chain at the lactam ring, and scalalactams C and D (3 and 4) possess a phenethyl group at the lactam ring moiety. Scalalactams Aâ»D (1â»4) did not show FXR antagonistic activity nor cytotoxicity up to 100 µM.
Asunto(s)
Poríferos/química , Sesterterpenos/química , Sesterterpenos/farmacología , Animales , Organismos Acuáticos/química , Evaluación Preclínica de Medicamentos/métodos , Humanos , Lactamas/química , Espectroscopía de Resonancia Magnética , Estructura Molecular , Receptores Citoplasmáticos y Nucleares/antagonistas & inhibidoresRESUMEN
HPLC-UV guided isolation of the culture broth of a marine bacterium Saccharomonospora sp. CNQ-490 has led to the isolation of two new natural products, lodopyridones B and C (1 and 2) along with the previously reported lodopyridone A (3). Their chemical structures were established from the interpretation of 2D NMR spectroscopic data and the comparison of NMR data with the lodopyridone A (3). Lodopyridones B and C (1 and 2) possess the thiazole, and chloroquinoline groups which are characteristic features of these molecules. Lodopyridones A-C show weak inhibitory activities on the ß-site amyloid precursor protein cleaving enzyme 1 (BACE1).
Asunto(s)
Actinobacteria/metabolismo , Sedimentos Geológicos/microbiología , Piridonas/química , Alcaloides/química , Alcaloides/aislamiento & purificación , Alcaloides/farmacología , Secretasas de la Proteína Precursora del Amiloide/antagonistas & inhibidores , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Péptidos beta-Amiloides/metabolismo , Línea Celular Tumoral , Activación Enzimática/efectos de los fármacos , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/aislamiento & purificación , Inhibidores Enzimáticos/farmacología , Humanos , Espectroscopía de Resonancia Magnética , Conformación Molecular , Neuronas/citología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Fragmentos de Péptidos/metabolismo , Piridonas/aislamiento & purificación , Piridonas/farmacologíaAsunto(s)
Síndrome Coronario Agudo , Hipertensión , Humanos , Rosuvastatina Cálcica/uso terapéutico , Síndrome Coronario Agudo/tratamiento farmacológico , Imidazoles/uso terapéutico , Tetrazoles/uso terapéutico , Hipertensión Esencial/tratamiento farmacológico , Quimioterapia Combinada , Hipertensión/tratamiento farmacológico , Antihipertensivos/uso terapéutico , Presión Sanguínea , Resultado del TratamientoRESUMEN
Intensive study of the organic extract of the marine-derived bacterium Saccharomonospora sp. CNQ-490 has yielded three new α-pyrones, saccharomonopyrones A-C (1-3). The chemical structures of these compounds were assigned from the interpretation of 1D, 2D NMR and mass spectrometry data. Saccharomonopyrone A (1) is the first α-pyrone microbial natural product bearing the ethyl-butyl ether chain in the molecule, while saccharomonopyrones B and C possess unusual 3-methyl and a 6-alkyl side-chain within a 3,4,5,6-tetrasubstituted α-pyrone moiety. Saccharomonopyrone A exhibited weak antioxidant activity using a cation radical scavenging activity assay with an IC50 value of 140 µM.
Asunto(s)
Actinomycetales/química , Productos Biológicos/aislamiento & purificación , Sedimentos Geológicos/química , Pironas/aislamiento & purificación , Productos Biológicos/química , Biología Marina , Estructura Molecular , Pironas/químicaRESUMEN
Three new structurally related depsipeptides, halicylindramides F-H (1-3), and two known halicylindramides were isolated from a Petrosia sp. marine sponge collected off the shore of Youngdeok-Gun, East Sea, Republic of Korea. Their planar structures were elucidated by extensive spectroscopic data analyses including 1D and 2D NMR data as well as MS data. The absolute configurations of halicylindramides F-H (1-3) were determined by Marfey's method in combination with Edman degradation. The absolute configurations at C-4 of the dioxyindolyl alanine (Dioia) residues of halicylindramides G (2) and H (3) were determined as 4S and 4R, respectively, based on ECD spectroscopy. The C-2 configurations of Dioia in 2 and 3 were speculated to both be 2R based on the shared biogenesis of the halicylindramides. Halicylindramides F (1), A (4), and C (5) showed human farnesoid X receptor (hFXR) antagonistic activities, but did not bind directly to hFXR.