ABSTRACT
Phytochemicals from the genus, Fagonia, have been attracting increasing attention due to their potential beneficial effects on human health. Fagonia species contain various types of phytochemicals such as flavonoids, alkaloids, saponins, terpenoids, coumarins and tannins. In this study, we investigated the phytochemical composition of unhydrolyzed and acid-hydrolyzed extracts of Fagonia indica and their bioactivity toward breast cancer MCF-7 cells in vitro. The results revealed that F. indica contains phytochemicals consistent with the reported phytochemical composition of this Fagonia species, with greater amounts of aglycones detected in the hydrolyzed extract. The crude extract of F. indica without acid hydrolysis was found to be ineffective in inhibiting the growth of MCF-7 cells at doses below 1000 µg/mL. However, after acid hydrolysis (to mimic gastro-intestinal hydrolysis), the F. indica extract became growth-inhibitory to MCF-7 cells as low as 10 µg/mL and the cytotoxicity increased with increasing dose and time of treatment. The results suggest that F. indica extracts contain phytochemicals in glycosidic forms whose aglycones are active as anti-proliferative agents toward breast cancer cells in vitro.
ABSTRACT
As a result of the first study on secondary metabolites from the cosmopolitan bioluminescent marine tube polychaete Chaetopterus variopedatus, a new bicyclic guanidine alkaloid, 6-epi-monanchorin (1), along with the previously known monanchorin (2) were isolated. The structure of 1 was elucidated by spectroscopic and chemical methods, including a cleavage of the C1-07 bond to obtain a secondary alcohol (3), which was used to determine the absolute configurations by Mosher's method. It was found that 1 and 2 were mainly accumulated in a secreted mucus special organ of the worm (food net), where green and blue-green microalgae were detected. A biosynthetic pathway to 6-epi-monanchorin and monanchorin from dietary polyeic fatty acid precursors was proposed.
Subject(s)
Bridged Bicyclo Compounds, Heterocyclic/analysis , Guanidines/analysis , Polychaeta/chemistry , Animals , Cell Line, Tumor , Humans , Molecular Structure , Secondary Metabolism , Tissue DistributionABSTRACT
Two new natural products, 6-bromogramine (1) and bis-6-bromogramine (2) were isolated from the marine hydroid A bietinaria abietina and their structures were established using NMR and MS analysis. Compounds 1 and 2 activate NF-cB-dependent transcriptional activity in JB6 Cl 41 NF-KB cells at 1.6 AM concentrations.
Subject(s)
Hydrozoa/chemistry , Indole Alkaloids/chemistry , NF-kappa B/metabolism , Animals , Biological Products/chemistry , Humans , Indole Alkaloids/isolation & purification , KB Cells , Molecular StructureABSTRACT
The new pentacyclic guanidine alkaloids, monanchoxymycalin A (1) and monanchoxymycalin B (2) were isolated from the Far-Eastern marine sponge Monanchora pulchra. Their structures were assigned on the basis of detailed analysis of lD- and 2D-NMR spectroscopic and mass spectrometric data. Compounds 1 and 2 exhibited potent cytotoxic activities against cervical epithelioid carcinoma HeLa cells and breast adenocarcinoma MDA-MB231 cells.
Subject(s)
Alkaloids/isolation & purification , Antineoplastic Agents/isolation & purification , Guanidines/isolation & purification , Porifera/chemistry , Alkaloids/chemistry , Alkaloids/pharmacology , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Survival/drug effects , Guanidines/chemistry , Guanidines/pharmacology , HumansABSTRACT
Although various anticancer drugs have been developed for the treatment of nonsmall cell lung cancer, chemotherapeutic efficacy is still limited. Natural products such as phytochemicals have been screened as novel alternative materials, but alternative funds such as marine bioresources remain largely untapped. Of these resources, marine sponges have undergone the most scrutiny for their biological activities, including antiinflammatory, antiviral, and anticancer properties. However, the biological mechanisms of the activities of these marine sponges are still unclear. We investigated the anticancer activity of marine sponges collected from Kosrae in Micronesia and examined their mechanisms of action using nonsmall cell lung cancer A549 cells as a model system. Of 20 specimens, the Haliclona sp. (KO1304-328) showed both dose- and time-dependent cytotoxicity. Further, methanol extracts of Haliclona sp. significantly inhibited cell proliferation and cell viability. A549 cells treated with Haliclona sp. demonstrated induced expression of c-Jun N-terminal kinase (JNK), p53, p21, caspase-8, and caspase-3. The percentage of apoptotic cells significantly increased in A549 cultures treated with Haliclona sp. These results indicate that Haliclona sp. induces apoptosis via the JNK-p53 pathway and caspase-8, suggesting that this marine sponge is a good resource for the development of drugs for treatment of nonsmall cell lung cancer.
ABSTRACT
A new pentacyclic guanidine alkaloid, monanchomycalin C (1), along with the earlier known ptilomycalin A (2), were isolated from the Far-Eastern marine sponge Monanchora pulchra. The structure of 1 was elucidated using 1D and 2D NMR spectroscopic and ma ss spectrometric da ta. Compounds 1 and 2 exhibited cytotoxic activities against human breast cancer MDA-MB-231 cells with IC50 values of 8.2 microM and 4.3 pM, respectively.
Subject(s)
Antineoplastic Agents/isolation & purification , Guanidine/analogs & derivatives , Porifera/chemistry , Animals , Antineoplastic Agents/chemistry , Cell Line, Tumor , Drug Screening Assays, Antitumor , Guanidine/chemistry , Guanidine/isolation & purification , Humans , Molecular Structure , RussiaABSTRACT
New marine natural products, pulchranins B and C (2 and 3), were isolated from the marine sponge Monanchora pulchra and their structures were established using NMR and MS analysis. Compounds 2 and 3 were moderately active as inhibitors of TRPV1 (EC50 value of 95 and 183 microM, respectively) and less potent against TRPV3 and TRPA1 receptors.
Subject(s)
Alkaloids/isolation & purification , Guanidines/isolation & purification , Porifera/chemistry , TRPV Cation Channels/antagonists & inhibitors , Alkaloids/chemistry , Animals , Guanidines/chemistry , Molecular Structure , Pacific OceanABSTRACT
Terminalia chebula (TC) is native to southern Asia to southwestern China and is used in traditional medicine for the treatment of human ailments including malignant tumors and diabetes. This plant also has antibacterial and immunomodulatory properties. Nuclear factor kappa-light chain-enhancer of activated B cells (NF-κB) is responsible for the expression of numerous genes involved in cell survival, proliferation, angiogenesis, inflammation, invasion and metastasis, among other processes. This study aims to assess the NF-κB inhibitory effect of TC extract in human lymphoblastic T (Jurkat) cells. The effects of TC extract were investigated using the FRET-based Gene Blazer technique in transfected Jurkat-NF-κB-RE-bla cells. The concentration of TC extract required for NF-κB inhibition was determined by a cell proliferation assay. Treatment with TC extract (50 µg/mL) inhibited NF-κB activity and protected against IκBα degradation and strongly suppressed IκBα phosphorylation in Jurkat-NF-κB-RE-bla cells. This treatment might be crucial for inhibiting NF-κB translocation and activation. In addition, the TC extract downregulated certain NF-κB regulated genes, including IL-8 and MCP-1, in Jurkat-NF-κB-RE-bla cells. Moreover, gallic acid was identified from the TC extract demonstrating its ability to inhibit NF-κB activity in Jurkat-NF-κB-RE-bla cells. Further studies to identify the role of gallic acid in NF-κB inhibition may uncover the crucial antiinflammatory and antitumor properties of the TC extract.
Subject(s)
Gallic Acid/pharmacology , NF-kappa B/antagonists & inhibitors , T-Lymphocytes/drug effects , Terminalia/chemistry , Animals , Humans , Jurkat Cells , Mice , NF-kappa B/metabolism , Plant Extracts/pharmacology , T-Lymphocytes/metabolismABSTRACT
Guided by the inhibitory activities of indole-containing natural products against isocitrate lyase (ICL) from Candida albicans and sortase A (SrtA) from Staphylococcus aureus, a series of compounds structurally analogous to natural products were synthesized. Eight SrtA inhibitors and an ICL inhibitor having higher activities than the natural products were discovered by screening the enzyme inhibitory activities of synthesized compounds. Among the SrtA inhibitors discovered, six exhibited higher activities than p-hydroxymercuribenzoic acid, which suggests that these compounds have great potential as alternative antibacterial agents.
Subject(s)
Aminoacyltransferases/antagonists & inhibitors , Anti-Bacterial Agents/chemistry , Bacterial Proteins/antagonists & inhibitors , Biological Products/chemistry , Indoles/chemistry , Isocitrate Lyase/antagonists & inhibitors , Anti-Bacterial Agents/pharmacology , Candida albicans/enzymology , Cysteine Endopeptidases , Drug Evaluation, Preclinical/methods , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacology , Indoles/chemical synthesis , Indoles/pharmacology , Staphylococcus aureus/enzymology , Structure-Activity RelationshipABSTRACT
The antioxidant activities of the ethanol (EtOH) extracts from the green seaweeds Enteromorpha compressa, Capsosiphon fulvescens, Chaetomorpha moniligera, and Ulva pertusa, as well as their solvent-partitioned fractions, were investigated, and their antioxidant activities were correlated with total phenolic and flavonoid contents. The EtOH extracts and their solvent-partitioned fractions showed 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl (OHâ¢) radical scavenging activities with strong reducing ability. The most effective antioxidant properties were observed from the EtOH extracts of E. compressa and C. fulvescens. Among the solvent-partitioned fractions obtained with n-hexane, chloroform (CF), and ethyl acetate, the CF fractions from E. compressa and C. fulvescens exhibited higher radical scavenging activities and stronger reducing ability than other fractions. The OH⢠radical scavenging capacity and reducing power of these fractions were comparable to those of a positive control, α-tocopherol, at concentrations of 0.06-1.0 mg/mL. Total phenolic contents showed little correlation (r²=0.22-0.42) with the antioxidant properties; however, significant correlation (r² =0.73-0.96) was observed with flavonoid contents, implying that the flavonoid constituents contribute substantially to the antioxidant properties of the extracts. The overall results suggested that the green seaweeds (E. compressa and C. fulvescens), especially their CF fractions, could be good sources of natural antioxidants and of highly beneficial ingredients for healthcare products, such as nutraceuticals, supplements, and cosmeceuticals.
Subject(s)
Antioxidants/pharmacology , Plant Extracts/pharmacology , Seaweed/chemistry , Biphenyl Compounds , Chemical Fractionation , Ethanol , Flavonoids/analysis , Free Radical Scavengers , Hydroxyl Radical , Oxidation-Reduction , Phenols/analysis , Picrates , Plant Extracts/chemistry , SolventsABSTRACT
Two sesterterpene sulfates (1-2) were isolated from tropical sponge Hippospongia sp. and their inhibitory activities against isocitrate lyase (ICL) from the rice blast fungus Mgnaporthe grisea were evaluated. Compound 3 was obtained by hydrolysis of compound 1. Compounds 1 and 3 were found to be potent ICL inhibitors, which inhibited appressorium formation and C(2) carbon utilization in M. grisea. Our results suggest that ICL plays crucial role in appressorium formation of M. grisea and is a new target for the protection of rice blast disease.