RESUMO
Scorpions, a group of oldest animals with wide distribution in the world, have a long history of medicinal use. Scorpio, the dried body of Buthus martensii, is a rare animal medicine mainly used for the treatment of liver diseases, spasm, and convulsions in children in China. The venom has been considered as the active substance of scorpions. However, little is known about the small molecules in the venom of scorpions. According to the articles published in recent years, scorpions contain amino acids, fatty acids, steroids, and alkaloids, which endow scorpions with antimicrobial, anticoagulant, metabolism-regulating, and antitumor activities. This paper summarizes the small molecule chemical components and pharmacological activities of scorpions, with a view to providing valuable information for the discovery of new active molecules and the clinical use of scorpions.
Assuntos
Animais Peçonhentos , Anti-Infecciosos , Venenos de Escorpião , Animais , Criança , Humanos , Peptídeos/química , Escorpiões/química , Escorpiões/metabolismo , DNA Complementar , Venenos de Escorpião/farmacologiaRESUMO
Lepista sordida is an edible mushroom possessing high nutritional value and high medicinal value. The artificial cultivation technology of L. sordida made a breakthrough and has been popularized in Yunnan, Guizhou, Sichuan province with good economic benefits. The secondary metabolites were investigated from ethyl EtOAc (acetate extract) of solid cultures of L. sordida. Silica gel column chromatography, semi-preparation HPLC, recrystallization, and medium pressure column chromatography were applied to obtain 15 compounds. Nine compounds were first isolated from genus Lepista and 11 compounds were first isolated from species L. sordida. Moreover, compounds 13 and 14 exhibited strong scavenging activity of ABTS.
Assuntos
Agaricales , Basidiomycota , China , Basidiomycota/químicaRESUMO
We have previously shown deep-sea-derived Streptomyces koyangensis SCSIO 5802 to produce two types of active secondary metabolites, abyssomicins and candicidins. Here, we report the complete genome sequence of S. koyangensis SCSIO 5802 employing bioinformatics to highlight its potential to produce at least 21 categories of natural products. In order to mine novel natural products, the production of two polycyclic tetramate macrolactams (PTMs), the known 10-epi-HSAF (1) and a new compound, koyanamide A (2), was stimulated via inactivation of the abyssomicin and candicidin biosynthetic machineries. Detailed bioinformatics analyses revealed a PKS/NRPS gene cluster, containing 6 open reading frames (ORFs) and spanning ~16 kb of contiguous genomic DNA, as the putative PTM biosynthetic gene cluster (BGC) (termed herein sko). We furthermore demonstrate, via gene disruption experiments, that the sko cluster encodes the biosynthesis of 10-epi-HSAF and koyanamide A. Finally, we propose a plausible biosynthetic pathway to 10-epi-HSAF and koyanamide A. In total, this study demonstrates an effective approach to cryptic BGC activation enabling the discovery of new bioactive metabolites; genome mining and metabolic profiling methods play key roles in this strategy.
Assuntos
Lactamas Macrocíclicas/metabolismo , Streptomyces , Organismos Aquáticos , Genoma , Humanos , Família Multigênica , Fitoterapia , Sequenciamento Completo do GenomaRESUMO
Two new natural diols, (2S, 3S, 4S)-4-methyl-1-phenylhexane-2,3-diol (1) and (2S, 3S)-4-methyl-1-phenylpentane-2,3-diol (2), together with five known compounds, xenocyloins B-D (3-5), lumichrome (6) and thymidine (7) were isolated from Streptomyces sp. CB09001. The absolute configurations of 1 and 2 were established by crystallographic structure analysis. The anti-inflammatory effects of 1-7 were also investigated in RAW246.7 murine macrophage cells stimulated by lipopolysaccharide. The indole derivative xenocyloin B (3) significantly inhibited inducible nitric oxide synthase expression in RAW264.7 cells and could be a potential anti-inflammatory drug lead.
Assuntos
Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Streptomyces/química , Animais , Cristalografia por Raios X , Avaliação Pré-Clínica de Medicamentos , Flavinas/química , Flavinas/farmacologia , Indóis/química , Indóis/farmacologia , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/metabolismo , Células RAW 264.7 , Streptomyces/metabolismoRESUMO
Grincamycins (GCNs) are a class of angucycline glycosides isolated from actinomycete Streptomyces strains that have potent antitumor activities, but their antitumor mechanisms remain unknown. In this study, we tried to identify the cellular target of grincamycin B (GCN B), one of most dominant and active secondary metabolites, using a combined strategy. We showed that GCN B-selective-induced apoptosis of human acute promyelocytic leukemia (APL) cell line NB4 through increase of ER stress and intracellular reactive oxygen species (ROS) accumulation. Using a strategy of combining phenotype, transcriptomics and protein microarray approaches, we identified that isocitrate dehydrogenase 1(IDH1) was the putative target of GCN B, and confirmed that GCNs were a subset of selective inhibitors targeting both wild-type and mutant IDH1 in vitro. It is well-known that IDH1 converts isocitrate to 2-oxoglutarate (2-OG), maintaining intracellular 2-OG homeostasis. IDH1 and its mutant as the target of GCN B were validated in NB4 cells and zebrafish model. Knockdown of IDH1 in NB4 cells caused the similar phenotype as GCN B treatment, and supplementation of N-acetylcysteine partially rescued the apoptosis caused by IDH1 interference in NB4 cells. In zebrafish model, GCN B effectively restored myeloid abnormality caused by overexpression of mutant IDH1(R132C). Taken together, we demonstrate that IDH1 is one of the antitumor targets of GCNs, suggesting wild-type IDH1 may be a potential target for hematological malignancies intervention in the future.
Assuntos
Antraquinonas/farmacologia , Antineoplásicos/farmacologia , Inibidores Enzimáticos/farmacologia , Glicosídeos/farmacologia , Isocitrato Desidrogenase/antagonistas & inibidores , Animais , Antraquinonas/metabolismo , Antineoplásicos/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Inibidores Enzimáticos/metabolismo , Glicosídeos/metabolismo , Humanos , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/metabolismo , Ácidos Cetoglutáricos/metabolismo , Simulação de Acoplamento Molecular , Mutação , Ligação Proteica , Espécies Reativas de Oxigênio/metabolismo , Peixe-ZebraRESUMO
Three new angucycline glycosides, designated grincamycin I (1: ), J (2: ), and K (3: ), together with the known congener A-7884 (4: ), were isolated from marine-derived actinomycete Streptomyces lusitanus SCSIO LR32. The structures of the new compounds were elucidated by comprehensive spectral data analysis. Compounds 2: and 4: exhibited antitumor activity against human cancer cells MDA-MB-435, MDA-MB-231, NCI-H460, HCT-116 and HepG2, and human normal breast epithelial cell MCF10A with IC50 values ranging from 0.4 to 6.9 µM. In addition, A-7884 (4: ) demonstrated antimicrobial activity against Micrococcus luteus with an MIC value of 1.95 µg/mL.
Assuntos
Antraquinonas/isolamento & purificação , Antineoplásicos/isolamento & purificação , Streptomyces/química , Antraquinonas/química , Antraquinonas/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Micrococcus luteus/efeitos dos fármacos , Estrutura MolecularRESUMO
Marine Actinobacteria are emerging as new resources for bioactive natural products with promise in novel drug discovery. In recent years, the richness and diversity of marine Actinobacteria from the South China Sea and their ability in producing bioactive products have been investigated. The objective of this work is to isolate and identify bioactive secondary metabolites from a marine actinobacterium SCSIO 1934 derived from sediments of South China Sea. The strain was identified as a Streptomyces spieces by analyzing its 16S rDNA sequence. Streptomyces sp. SCSIO 1934 was fermented under optimized conditions and seven bioactive secondary metabolites were isolated and purified by chromatographic methods including colum chromatography over silica gel and Sephadex LH-20. Their structures were elucidated as 17-O-demethylgeldanamycin (1), lebstatin (2), 17-O-demethyllebstatin (3), nigericin (4), nigericin sodium salt (5), abierixin (6), respectively, by detailed NMR spectroscopic data (1H, 13C, COSY, HSQC and HMBC). This work provided a new marine actinobacterium Streptomyces sp. SCSIO 1934, capable of producing diverse bioactive natural products.
Assuntos
Antibacterianos/química , Sedimentos Geológicos/microbiologia , Streptomyces/química , Streptomyces/classificação , China , DNA Ribossômico/química , DNA Ribossômico/genética , Oceanos e Mares , RNA Ribossômico 16S/genética , Streptomyces/genética , Streptomyces/isolamento & purificaçãoRESUMO
OBJECTIVE: To investigate the chemical constituents of Hemistepta lyrata. METHOD: The constituents of the EtOAc-soluble portions of the 95% ethanol extract were isolated and purified by means of chromatography. Compounds were identified by their physical characteristics and spectral features. RESULT: Five compounds were isolated and identified as caffeic acid (1), tracheloside (2), uracil (3), 8-carboxymethyl-p-hydroxycinnamic acid (4), and 3-O-p-coumaroylquinic acid (5). CONCLUSION: Compounds 1-5 were isolated from this genus for the first time.
Assuntos
4-Butirolactona/análogos & derivados , Asteraceae/química , Ácidos Cafeicos/isolamento & purificação , Glucosídeos/isolamento & purificação , Plantas Medicinais/química , Uracila/isolamento & purificação , 4-Butirolactona/química , 4-Butirolactona/isolamento & purificação , Ácidos Cafeicos/química , Glucosídeos/química , Uracila/químicaRESUMO
AIM: To study the chemical constituents of Cypripedium tibeticum. METHODS: Compounds were isolated by repeated silica gel chromatography and purified on Sephadex LH-20 and structures were determined by spectral analysis. RESULTS: Cypritibetquinones A and B were isolated from the ethyl acetate residue and their structures were determined as 7-hydroxy-2-methoxy-1 4-phenanthraquinone (1) and 7-hydroxy-2, 10-dimethoxy-l1 4-phenanthraquinone (2), respectively, by extensive spectral analyses. CONCLUSION: Cypritibetquinones A and B are two new phenanthraquinones.
Assuntos
Antraquinonas/isolamento & purificação , Orchidaceae/química , Fenantrenos/isolamento & purificação , Plantas Medicinais/química , Antraquinonas/química , Conformação Molecular , Estrutura Molecular , Fenantrenos/química , Rizoma/químicaRESUMO
Seven new cycloartane glycosides (1-7), beesiosides G, H, and J-N, together with beesioside I (8) and beesioside A, were isolated from the rhizomes of Beesia calthifolia, and their structures were established by spectroscopic and chemical methods. Beesiosides G, H, and J-N were assigned as 20xi(1),24xi(2)-epoxy-9,19-cyclolanostane-3beta,16beta,18,25-tetraol-3-O-beta-D-glucopyranoside (1), 20xi(1),24xi(2)-epoxy-9,19-cyclolanostane-3beta,16beta,18,25-tetraol-3-O-[beta-D-glucopyranosyl-(1-->6)]-beta-D-glucopyranoside (2), (20S,24R)-15alpha,16beta-diacetoxy-20,24-epoxy-9,19-cyclolanostane-3beta,18,25-triol-3-O-beta-D-xylopyranoside (3), (20S,24S)-16beta-acetoxy-18,24;20,24-diepoxy-9,19-cyclanostane-3beta,15beta,25-triol-3-O-beta-D-xylopyranoside (4), (20S,24S)-16beta-acetoxy-18,24;20,24-diepoxy-9,19-cyclanostane-3beta,25-diol-3-O-beta-D-xylopyranoside (5), 20xi(1),24xi(2)-epoxy-15alpha-acetoxy-9,19-cyclolanostane-3beta,16beta,25-triol-3-O-beta-D-xylopyranoside (6), and 20xi(1),24xi(2)-epoxy-9,19-cyclolanostane-3beta,12alpha,15alpha,16beta,25-pentaol-3-O-beta-D-xylopyranoside (7), respectively.
Assuntos
Glicosídeos/isolamento & purificação , Plantas Medicinais/química , Ranunculaceae/química , Saponinas/isolamento & purificação , Triterpenos/isolamento & purificação , Cromatografia em Camada Fina , Cristalografia por Raios X , Glicosídeos/química , Hidrólise , Medicina Tradicional Chinesa , Conformação Molecular , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Saponinas/química , Espectrofotometria Infravermelho , Estereoisomerismo , Triterpenos/químicaRESUMO
Six new cycloartane triterpene glycosides (1-6), beesiosides A-F, were isolated from whole plants of Beesia calthaefolia, and their structures were elucidated on the basis of extensive NMR experiments and chemical methods. Beesiosides A-F were assigned as (20S,24R)-epoxy-9,19-cyclolanostane-3beta,16beta,18,25-tetraol-3-O-beta-D-xylopyranoside (1), (20S,24R)-epoxy-9,19-cyclolanostane-3beta,12beta,16beta,18,25-pentaol-3-O-beta-D-xylopyranoside (2), (20S,24R)-epoxy-9,19-cyclolanostane-3beta,12alpha,16beta,18,25-pentaol-3-O-beta-D-xylopyranoside (3), (20S,24R)-16beta-acetoxy-20,24-epoxy-9,19-cyclolanostane-3beta,12alpha,18,25-tetraol-3-O-beta-D-xylopyranoside (4), (20S,24R)-epoxy-9,19-cyclolanostane-3beta,15alpha,16beta,18,25-pentaol-3-O-beta-D-xylopyranoside (5), and (20S,24R)-16beta-acetoxy-20,24-epoxy-9,19-cyclolanostane-3beta,12beta,25-triol-3-O-beta-D-xylopyranoside (6), respectively.
Assuntos
Glicosídeos/isolamento & purificação , Plantas Medicinais/química , Ranunculaceae/química , Saponinas/isolamento & purificação , Triterpenos/isolamento & purificação , Cromatografia em Camada Fina , Glicosídeos/química , Hidrólise , Medicina Tradicional Chinesa , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Saponinas/química , Espectrofotometria Infravermelho , Estereoisomerismo , Triterpenos/químicaRESUMO
AIM: To investigate the chemical constituents of the rhizomes of Beesia calthaefolia native to China in order to obtain a more comprehensive understanding of its effective components. METHODS: Compounds were isolated by column chromatography with silica gel. Their structures were elucidated by spectral analysis and chemical evidence. Compounds identified were subjected to pharmacological evaluation. RESULTS: Two novel compounds were isolated and identified as (20S, 24S)-15 alpha-acetoxy-16 beta, 24; 20, 24-diepoxy-9, 19-cyclolanostane-3 beta, 25-diol-3-O-beta-D-xylopyranoside (I) and (20S, 24R)-15 alpha-acetoxy-9, 19-cyclolanostane-3 beta, 16 beta, 20, 24, 25-pentaol-3-O-beta-D-xylopyranoside (II), named beesioside O and beesioside P. CONCLUSION: Compounds I and II are new compounds. Compounds I exhibited immunosuppressive activity and could inhibit angiogenesis as well as inhibit the proliferation of osteoblast. Compound II displayed remarkable inhibition activity against calcium channel receptor.