Genome Characteristics of the Endophytic Fungus Talaromyces sp. DC2 Isolated from Catharanthus roseus (L.) G. Don.

Talaromyces sp. DC2 is an endophytic fungus that was isolated from the stem of Catharanthus roseus (L.) G. Don in Hanoi, Vietnam and is capable of producing vinca alkaloids. This study utilizes the PacBio Sequel technology to completely sequence the whole genome of Talaromyces sp. DC2The genome study revealed that DC2 contains a total of 34.58 Mb spanned by 156 contigs, with a GC content of 46.5%. The identification and prediction of functional protein-coding genes, tRNA, and rRNA were comprehensively predicted and highly annotated using various BLAST databases, including non-redundant (Nr) protein sequence, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Clusters of Orthologous Groups (COG), and Carbohydrate-Active Enzymes (CAZy) databases. The genome of DC2 has a total of 149, 227, 65, 153, 53, and 6 genes responsible for cellulose, hemicellulose, lignin, pectin, chitin, starch, and inulin degradation, respectively. The Antibiotics and Secondary Metabolites Analysis Shell (AntiSMASH) analyses revealed that strain DC2 possesses 20 biosynthetic gene clusters responsible for producing secondary metabolites. The strain DC2 has also been found to harbor the DDC gene encoding aromatic L-amino acid decarboxylase enzyme. Conclusively, this study has provided a comprehensive understanding of the processes involved in secondary metabolites and the ability of the Talaromyces sp. DC2 strain to degrade plant cell walls.

Draft genome sequencing of halotolerant bacterium Salinicola sp. DM10 unravels plant growth-promoting potentials.

In this study, strain DM10 was isolated from mangrove roots and characterized as a halotolerant plant growth-promoting bacterium. Strain DM10 exhibited the ability to solubilize phosphate, produce siderophore, show 1-aminocyclopropane-1-carboxylic acid deaminase activity, and hydrolyze starch. The rice plants subjected to a treatment of NaCl (200 mM) and inoculated with strain DM10 showed an improvement in the shoot length, root length, and dried weight, when compared to those exposed solely to saline treatment. The comprehensive genome sequencing of strain DM10 revealed a genome spanning of 4,171,745 bp, harboring 3626 protein coding sequences. Within its genome, strain DM10 possesses genes responsible for both salt-in and salt-out strategies, indicative of a robust genetic adaptation aimed at fostering salt tolerance. Additionally, the genome encodes genes involved in phosphate solubilization, such as the synthesis of gluconic acid, high-affinity phosphate transport systems, and alkaline phosphatase. In the genome of DM10, we identified the acdS gene, responsible for encoding 1-aminocyclopropane-1-carboxylate deaminase, as well as the amy1A gene, which encodes α-amylase. Furthermore, the genome of DM10 contains sequences associated with the iron (3+)-hydroxamate and iron uptake clusters, responsible for siderophore production. Such data provide a deep understanding of the mechanism employed by strain DM10 to combat osmotic and salinity stress, facilitate plant growth, and elucidate its molecular-level behaviors.

Insights into Structural Behaviors of Thiolated and Aminated Reduced Graphene Oxide Supports to Understand Their Effect on MOR Efficiency.

It is essential to develop novel catalysts with high catalytic activity, strong durability, and good stability for further application in methanol fuel cells. In this work, we present for the first time the effect of the chemical functional groups (thiol and amine) with different electron affinity in reduced graphene oxide supports on the morphology and catalytic activity of platinum nanoparticles for the methanol oxidation reaction. Hydroxyl groups on graphene oxide were initially brominated and then transformed to the desired functional groups. The good dispersion of metal nanoparticles over functionalized carbon substrates (particle size less than 5 nm) with good durability, even at a limited functionalization degree (less than 7%) has been demonstrated by morphological and structural studies. The durability of the catalysts was much improved via strong coordination between the metal and nitrogen or sulfur atoms. Impressively, the catalytic activity of platinum nanoparticles on aminated reduced graphene oxide was found to be much better than that on thiolated graphene oxide despite the weaker affinity between amine and noble metals. These findings support further developing new graphene derivatives with the desired functionalization for electronics and energy applications..

Sensing interface based on electrodeposited Cu-BTC microporous film for electrochemical detection of the painkiller paracetamol.

The use of metal-organic framework materials in electrochemical sensors has been gaining more attention in the last few years due to their highly porous structure and electrocatalytic activity. In this work, a novel paracetamol electrochemical sensor based on a Cu-BTC microporous film electrochemically grown onto glassy carbon electrode was introduced. The Cu-BTC film was deposited directly onto the electrode surface via an electrochemical approach using a Et3N probase to accelerate the growth of Cu-BTC. The fast growth enables the formation of a microporous structure with better adsorption of targeted molecules. The two-dimensional arrangement of units made of dimeric copper cations coordinated to carboxylate anions helped to improve the electrochemical conductivity and electron transfer rate at the electrode surface (charge transfer resistance was dramatically decreased from 2173 Ω to 86 Ω). The electrocatalytic activity of copper ion centers in Cu-BTC was studied with peak separation between oxidation and reduction peaks of pseudo-redox paracetamol molecules much shortened (from 629 mV to 87 mV). Consequently, the sensing parameters (sensitivity and detection limit) of the as-prepared paracetamol sensor were considerably improved. Further works need to be conducted on tailoring ligand structure in order to much improve the electrical conductivity of metal-organic frameworks for sensing purposes.

A novel bimetallic MOFs combined with gold nanoflakes in electrochemical sensor for measuring bisphenol A.

In this paper, a novel bimetallic Fe-Cu metal-organic framework combined with 1,3,5-benzenetricarboxylic acid (Fe-Cu-BTC) are synthesized using hydrothermal reaction. The bimetallic Fe-Cu-BTC with high BET (1504 cm3 g-1) and high Langmuir surface area (1831 cm3 g-1) is composited by gold nanoparticles to improve the conductivity and to develop their synergistic effect. A novel bisphenol A (BPA) sensor was prepared by dropcasting Fe-Cu-BTC on glassy carbon electrodes (GCE) followed by AuNPs electrodeposition. The Fe-Cu-BTC framework were characterized by X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy studies (TEM), FT-IR, BET measurements and EDX spectra. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) were carried out for surveying the electrochemical properties of the sensors and for the quantification of BPA. Two linear ranges of BPA concentrations 0.1-1.0 µM and 1.0-18 µM with 18 nM limit of detection were obtained. The developed sensor was used to measure the concentration of BPA in samples extracted from rain coat with the recovery ranging from 85.70 to 103.23%.

Anti-neuroinflammatory effect of oxaline, isorhodoptilometrin, and 5-hydroxy-7-(2'-hydroxypropyl)-2-methyl-chromone obtained from the marine fungal strain Penicillium oxalicum CLC-MF05.

Penicillium is a rich source of bioactive compounds. Among all Penicillium species, Penicillium oxalicum has been reported to produce various types of secondary metabolites, including alkaloids, phenolics, and tetrahydroxanthone dimeric compounds, exhibiting many pharmacological effects, such as antiviral, antibacterial, and cytotoxic activities. Three secondary metabolites were isolated from a fermented culture of the sponge-associated fungal strain P. oxalicum CLC-MF05: oxaline (1), isorhodoptilometrin (2), and 5-hydroxy-7-(2'-hydroxypropyl)-2-methyl-chromone (3). Their chemical structures were identified by 1D and 2D NMR and high-resolution mass spectroscopic analyses and compared with previously reported data. All three compounds inhibited NO and PGE2 overproduction and iNOS and COX-2 overexpression in both LPS-stimulated BV2 and rat primary microglia. These metabolites also repressed mRNA expression of TNF-α, IL-1ß, IL-6, and IL-12. Further, mechanistic studies revealed that the inhibitory actions of compounds 1-3 were regulated by the inactivation of the NF-κB and MAPK signaling pathways. Furthermore, inactivation of the TLR4/MyD88 pathway contributed to the anti-neuroinflammatory activity of these compounds. These results suggest that compounds 1-3 represent potential anti-inflammatory candidates for the treatment of neurodegenerative diseases; however, further investigation is needed.

Secondary metabolites from a peanut-associated fungus Aspergillus niger IMBC-NMTP01 with cytotoxic, anti-inflammatory, and antimicrobial activities.

Chemical investigation of a peanut-associated fungal strain Aspergillus niger IMBC-NMTP01 resulted in isolation and identification of 14 secondary metabolites, including two new, epi-aspergillusol (1) and aspernigin (3), and 12 known compounds: pyrophen (2), 2-(hydroxyimino)-3-(4-hydroxyphenyl)propanoic acid (4), aspergillusol A (5), rubrofusarin B (6), nigerasperone A (7), fonsecin (8), TMC-256C1 (9), pyranonigrin A (10), orlandin (11), nigerasperone C (12), asperpyrone A (13), and 5-(hydroxymethyl)-2-furancarboxylic acid (14). Compounds 9, 12-14 showed cytotoxicity toward all six human cancer cell lines, including HepG2, KB, HL-60, MCF-7, SK-Mel2, and LNCaP, with IC50 values ranging from 8.4 to 84.5 µM, compounds 3-5 were cytotoxic against five cancer cell lines except HepG2, whereas 1 exhibited cytotoxicity toward HepG2, KB, and MCF-7 cells. All of the compounds, except 2 and 13, inhibited NO overproduction in LPS-induced RAW264.7 cells. In addition, all of the compounds displayed antimicrobial effects against Enterococcus faecalis, whereas 13 compounds, except 10, significantly inhibited the growth of the yeast Candida albicans.

Anti-inflammatory norclerodane diterpenoids and tetrahydrophenanthrene from the leaves and stems of Dioscorea bulbifera.

Chemical investigation of the leaves and stems of Dioscorea bulbifera resulted in isolation of 10 compounds, including three new norclerodane diterpenoids, diosbulbiferins A (1) and B (2) and diosbulbiferinoside A (3), and one new natural congener, diosbulbiferin C (4), along with one new tetrahydrophenanthrene, diosbulbinone (8). Their structures were elucidated by comprehensive analyses of spectroscopic methods, including NMR and mass spectra. The absolute configurations of compounds 1-3 and 8 were deduced by time-dependent density functional theory (TD-DFT) electronic circular dichroism (ECD) spectroscopic analyses. In addition, cytotoxic effects against MCF-7, HepG2, and SK-Mel-2 cancer cells and in vitro anti-inflammatory effects of the isolated compounds in LPS-stimulated BV2 microglial cells were also reported.

Cytotoxic and immunomodulatory phenol derivatives from a marine sponge-derived fungus Ascomycota sp. VK12.

Chemical investigation of the marine-derived endophytic fungus Ascomycota sp. VK12 resulted in isolation and identification of a new compound, (3R)-(3',5'-dihydroxyphenyl)butan-2-one (1) and five known ones: AGI-7 (2), sescandelin (3), sescandelin-B (4), 4-hydroxybenzaldehyde (5), and hydroxysydonic acid (6). The absolute configuration of 1 was determined by time-dependent density functional theory electronic circular dichroism, specific optical rotation, and NMR calculations. Compounds 1 and 2 showed cytotoxicity towards HepG2, MCF-7, and SK-Mel2 carcinoma cells, with IC50 values ranging from 48.6 to 96.5 µM. Compounds 1, 2, 4-6 displayed NO inhibitory effects in LPS-stimulated BV2 cells, with IC50 values in a range from 24.2 to 76.5 µM. Compound 2 further inhibited PGE2 overproduction, with an IC50 value of 25.3 µM. The inhibitory effects of 2 towards NO and PGE2 overproduction were found to have a close relationship with its suppression of iNOS and COX-2 protein expression, respectively.

Regulation of cell activation by A20 through STAT signaling in acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is the hematologic malignancy characterized by the aberrant proliferation of immature lymphoid cells. A20 is a deubiquitinase gene that inhibits functional activation of immune cells mediated through NF-κB/STAT pathways and frequently found inactivated in lymphoma. IL-6 is a pro-inflammatory cytokine secreted by immune cells under the pathogenic conditions and regulated by STAT signaling. Little is known about the role of A20 in regulating the function of ALL blasts and underlying molecular mechanisms. The present study, therefore, explored whether A20 expression contributes to IL-6 induced cell migration and activation of myeloid cells in ALL. To this end, blood samples of thirty-five adult ALL patients were examined. Gene expression profile was determined by quantitative RT-PCR, immunophenotype by flow cytometry, secretion of inflammatory cytokines by ELISA, and cell migration by a transwell migration assay. As a result, the expression of A20 was inactivated in ALL. Immunophenotypic analysis indicated that percent of CD11b+CD40+ expressing cells present in ALL was significantly reduced when transfected with PEM-T easy A20. Importantly, IL6-induced CXCL12-mediated migration of ALL blasts was dependent on the presence of A20. The inhibitory effects of A20 on activated myeloid cells and migration of ALL blasts were mediated through the STAT pathway upon IL-6 challenge. In addition, the CA-125 level was much higher in elderly females than either young female or male ALL patients or healthy donors. In conclusion, the inhibitory effects of A20 on activation of ALL blasts are expected to affect the immune response to treatment for adult ALL patients.

Transcriptome Sequencing and Analysis of Changes Associated with Insecticide Resistance in the Dengue Mosquito (Aedes aegypti) in Vietnam.

The mosquito Aedes aegypti is a transmission vector for dangerous epidemic diseases in humans. Insecticides have been used as the most general vector control method in the world. However, Ae. aegypti have developed many resistant mechanisms such as reduced neuronal sensitivity to insecticides (target-site resistance), enhanced insecticide metabolism (metabolic resistance), altered transport, sequestration, and other mechanisms. It has become a major problem for vector control programs. Transcriptome sequencing and bioinformatic analysis were used to compare transcription levels between a susceptible strain (Bora7) and a resistant strain (KhanhHoa7) collected from the field. A total of 161 million Illumina reads, including 66,076,678 reads from the Bora7 strain and 69,606,654 reads from the KhanhHoa7 strain, were generated and assembled into 11,174 genes. A comparison of the KhanhHoa7 transcriptome to that of Bora7 showed 672 upregulated genes and 488 downregulated genes. We identified the highly upregulated genes: cytochrome P450 4C1, 4C3, 4C21, 4D1, 4D1 isoform X2, 4D2, 4D2 isoform X2, 4G15, 6A2, 6A8, 6D3, and 9E2; Glutathione S transferase (GST1), UGT1-3, 1-7, 2B15, and 2B37; binding cassette transporter (ABC) transporter F family member 4 and ABC transporter G family member 20. Interestingly, there was a significant increase in the expression of the genes such as CYP9E2 (8.3-fold), CYP6A8 (5.9-fold), CYP6D3 (5.4-fold), CYP4C21 (5.4-fold), CYP4G15 (5.2-fold), GST1 (3.5-fold), and ABC transporter 4 (2.1-fold). Our results suggested a potential relationship between the expression of the genes in metabolic processes and insecticide resistance in the studied strain. These results may contribute to the understanding of the mechanisms of insecticide resistance in Ae. aegypti.

Oleanane-type Saponins from Glochidion hirsutum and Their Cytotoxic Activities.

Five new oleanane-type saponins, hirsutosides A - E, were isolated from the leaves of Glochidion hirsutum (Roxb.) Voigt. Their structures were elucidated as 21ß-benzoyloxy-3ß,16ß,23,28-tetrahydroxyolean-12-ene 3-O-ß-d-glucopyranoside (1), 21ß-benzoyloxy-3ß,16ß,23,28-tetrahydroxyolean-12-ene 3-O-ß-d-glucopyranosyl-(1 â†’ 3)-ß-d-glucopyranoside (2), 21ß-benzoyloxy-3ß,16ß,23,28-tetrahydroxyolean-12-ene 3-O-6-acetyl-[ß-d-glucopyranosyl-(1 â†’ 3)]-ß-d-glucopyranoside (3), 21ß-benzoyloxy-3ß,16ß,23,28-tetrahydroxyolean-12-ene 3-O-ß-d-glucopyranosyl-(1 â†’ 3)-〈-l-arabinopyranoside (4), and 21ß-benzoyloxy-3ß,16ß,23-trihydroxyolean-12-ene-28-al 3-O-ß-d-glucopyranosyl-(1 â†’ 3)-α-l-arabinopyranoside (5). All isolated compounds were evaluated for cytotoxic activities on four human cancer cell lines, HepG-2, A-549, MCF-7, and SW-626 using the SRB assay. Compounds 1, 2, 4, and 5 showed significant cytotoxic activities against all human cancer cell lines with IC50 values ranging from 3.4 to 10.2 µm. Compound 3 containing acetyl group at glc C(6″) exhibited weak cytotoxic activity with IC50 values ranging from 47.0 to 54.4 µm.

Anti-inflammatory effects of secondary metabolites isolated from the marine-derived fungal strain Penicillium sp. SF-5629.

After the chemical investigation of the ethyl acetate extract of the marine-derived fungal strain Penicillium sp. SF-5629, the isolation and structural elucidation of eight secondary metabolites, including (3R,4S)-6,8-dihydroxy-3,4,7-trimethylisocoumarin (1), (3S,4S)-sclerotinin A (2), penicitrinone A (3), citrinin H1 (4), emodin (5), ω-hydroxyemodin (6), 8-hydroxy-6-methyl-9-oxo-9H-xanthene-1-carboxylate (7), and 3,8-dihydroxy-6-methyl-9-oxo-9H-xanthene-1-carboxylate (8) were carried out. Evaluation of the anti-inflammatory activity of these metabolites showed that 4 inhibited nitric oxide and prostaglandin E2 production in lipopolysaccharide-stimulated BV2 microglia, with IC50 values of 8.1 ± 1.9 and 8.0 ± 2.8 µM, respectively. The inhibitory function of 4 was confirmed based on decreases in inducible nitric oxide synthesis and cyclooxygenase-2 gene expression. In addition, 4 was found to suppress the phosphorylation of inhibitor kappa B-α, interrupt the nuclear translocation of nuclear factor kappa B, and decrease the activation of p38 mitogen-activated protein kinase.

New Lignans from Antidesma hainanensis Inhibit NO Production in BV2 Microglial Cells.

Two new lignans (7S,7'R,8S,8'R)-3,3'-dimethoxy-7,7'-epoxylignan-4,4',9-triol 4-O-ß-D-glucopyranoside (1) and 9-O-formylaviculin (2) together with other thirteen known secondary metabolites were isolated from the leaves of Antidesma hainanensis. Their chemical structures were determined using NMR, electrospray ionization (ESI)-MS, circular dichroism (CD) spectroscopic methods, and as well as by comparison with those reported in the literature. Neuro-inflammatory activity of isolated compounds was evaluated by their inhibition on nitric oxide (NO) production in activated BV2 microglial cells. At concentration of 40 µM, compounds 1-3, 5, 7, 8, 9, 14, and 15 exhibited inhibitory effects over 50%, suggesting that they could be potential candidate drugs for the cure of neuro-inflammation. In addition, compounds 1, 8, 14, and 15 significantly inhibited 16.23, 27.76, 21.23, and 29.44% NO production at diluted concentration as low as 2.5 µM.

Anti-neuroinflammatory activities of indole alkaloids from kanjang (Korean fermented soy source) in lipopolysaccharide-induced BV2 microglial cells.

Kanjang (Korean soy sauce) is a byproduct of the production of the Korean fermented soybean. In the present study, seven indole alkaloid derivatives were isolated from methanol extract of kanjang. Their structures were identified as 1-propyl-1,2,3,4-tetrahydro-ß-carboline-3-carboxylic acid (1), 1-methyl-1,2,3,4-tetrahydro-ß-carboline-3-carboxylic acid (2), 1-methyl-1,2,3,4-tetrahydro-ß-carboline-1-carboxylic acid (3), 3-indoleacetic acid (4), Nb-acetyltryptamine (5), 1-methyl-3,4-dihydro-ß-carboline (6), and flazine (7) by NMR and MS analyses. Preliminary screening for anti-neuroinflammatory effects of isolated indole alkaloids in lipopolysaccharide (LPS)-stimulated BV2 cells revealed that these compounds inhibited the production of nitric oxide and prostaglandin E2. For the subsequent investigation of anti-neuroinflammatory action of these metabolites, compounds 4 and 7 were selected, and the results revealed that these inhibitory effects correlated with the suppressive effect of 4 and 7 on inducible nitric oxide synthase and cyclooxygenase-2 expression in LPS-stimulated BV2 cells. In regards to the mechanism of the anti-inflammatory effect, 4 and 7 significantly inhibited the nuclear factor-kappa B pathway.

Steroidal Glucosides from the Rhizomes of Tacca chantrieri and Their Inhibitory Activities of NO Production in BV2 Cells.

Two new steroidal glucosides, chantriolides D and E (1 and 2), along with four known compounds, chantriolide A (3), chantriolide B (4), chantriolide C (5), and (25S)-spirost-5-en-3-ol 3-O-α-L-rhamnopyranosyl-(1-->2)-O-[α-L-rhamnopyranosyl-(1-->3)]-ß-D-glucopyranoside (6) were isolated from the rhizomes of Tacca chantrieri. Their structures were determined by 1D and 2D NMR spectroscopic and HR-ESI-MS data, as well as by comparison with reported data. Compounds 1 and 2 were found to show strong inhibitory NO effect in BV2 cells, with IC50 values of 12.45 and 59.03 µM, respectively.

Dihydroisocoumarin Derivatives from Marine-Derived Fungal Isolates and Their Anti-inflammatory Effects in Lipopolysaccharide-Induced BV2 Microglia.

Chemical investigation of the EtOAc extracts of marine-derived fungal isolates Aspergillus sp. SF-5974 and Aspergillus sp. SF-5976 yielded a new dihydroisocoumarin derivative (1) and 12 known metabolites. The structures of the isolated metabolites were established by extensive spectroscopic analyses, including 1D and 2D NMR spectra and MS data. Among the metabolites, the absolute configuration of 5'-hydroxyasperentin (6) was determined by single-crystal X-ray diffraction analysis. The in vitro antineuroinflammatory effects of the metabolites were also evaluated in lipopolysaccharide (LPS)-stimulated microglial cells. Among the isolated metabolites, dihydroisocoumarin derivatives 1-6 (10-80 µM) were shown to inhibit LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production by suppressing the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), respectively, in LPS-stimulated BV2 microglia. Further, 1 (20-80 µM) was found to suppress the phosphorylation of the inhibitor of nuclear factor kappa B-α (IκB-α), interrupt the nuclear translocation of nuclear factor kappa B (NF-κB), and decrease the activation of p38 mitogen-activated protein kinase (MAPK).

Protein Tyrosine Phosphatase 1B Inhibitors from the Roots of Cudrania tricuspidata.

A chemical investigation of the methanol extract from the roots of Cudrania tricuspidata resulted in the isolation of 16 compounds, including prenylated xanthones 1-9 and flavonoids 10-16. Their structures were identified by NMR spectroscopy and mass spectrometry and comparisons with published data. Compounds 1-9 and 13-16 significantly inhibited PTP1B activity in a dose dependent manner, with IC50 values ranging from 1.9-13.6 µM. Prenylated xanthones showed stronger PTP1B inhibitory effects than the flavonoids, suggesting that they may be promising targets for the future discovery of novel PTP1B inhibitors. Furthermore, kinetic analyses indicated that compounds 1 and 13 inhibited PTP1B in a noncompetitive manner; therefore, they may be potential lead compounds in the development of anti-obesity and -diabetic agents.

Peroxisome proliferator-activated receptor transactivational effects in HepG2 cells of cembranoids from the soft coral Lobophytum crassum Von Marenzeller.

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that regulate the expression of multiple genes involved in metabolic, anti-inflammatory, and developmental processes. This study evaluated the PPARs transactivational effects of thirteen cembranoid diterpenoids 1-13 from the soft coral Lobophytum crassum, using PPAR-responsive elements-luciferase reporter and GAL4-PPAR chimera assays. All isolated compounds activated the transcription of PPARs in a dose-dependent manner, with EC50 values ranging from 2.07 ± 1.73 to 130.20 ± 1.85 µM. Moreover, compounds 6-9 affected the transactivation of all three PPAR types, PPARα, γ, ß(δ), in a dose-dependent manner, with EC50 values in a ranging from 11.92 ± 1.23 to 122.50 ± 2.12 µM. These results provide a scientific rationale for further studies on the soft coral L. crassum and its diterpenoid constituents to develop medicinal products against inflammatory and metabolic diseases.

Tanzawaic acid derivatives from a marine isolate of Penicillium sp. (SF-6013) with anti-inflammatory and PTP1B inhibitory activities.

Chemical investigation of a marine-derived fungus Penicillium sp. SF-6013 resulted in the discovery of a new tanzawaic acid derivative, 2E,4Z-tanzawaic acid D (1), together with four known analogues, tanzawaic acids A (2) and D (3), a salt form of tanzawaic acid E (4), and tanzawaic acid B (5). Their structures were mainly determined by analysis of NMR and MS data, along with chemical methods. Preliminary screening for anti-inflammatory effects in lipopolysaccharide (LPS)-activated microglial BV-2 cells showed that compounds 1, 2, and 5 inhibited the production of nitric oxide (NO) with IC50 values of 37.8, 7.1, and 42.5 µM, respectively. Compound 2 also inhibited NO production in LPS-stimulated RAW264.7 murine macrophages with an IC50 value of 27.0 µM. Moreover, these inhibitory effects correlated with the suppressive effect of compound 2 on inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in LPS-stimulated RAW264.7 and BV2 cells. In addition, compounds 2 and 5 significantly inhibited the activity of protein tyrosine phosphatase 1B (PTP1B) with the same IC50 value (8.2 µM).