Antimicrobial properties of unusual eremophilanes from the endophytic Diaporthe sp. BCC69512.

Six undescribed infrequent eremophilane derivatives including diaportheremopholins A - F and its previously undescribed side chain (E)-2-methyloct-2-enoic acid, together with three known compounds (testacein, xestodecalactones B and C), were isolated from the endophytic fungus Diaporthe sp. BCC69512. The chemical structures were determined based on NMR spectroscopic information in conjunction with the evidence from NOESY spectrum, Mosher's application, and chemical reactions for corroborating the absolute configurations. The isolated compounds were evaluated for biological properties such as antimalarial, anti-TB, anti-phytopathogenic fungal, antibacterial activities and for cytotoxicity against malignant (MCF-7 and NCI-H187) and non-malignant (Vero) cells. Diaportheremopholins B (2) and E (5) possessed broad antimicrobial activity against Mycobacterium tuberculosis, Bacillus cereus, Alternaria brassicicola and Colletotrichum acutatum with MICs in a range of 25.0-50.0 µg/mL. Testacein (7) exhibited strong anti-A. brassicicola and anti-C. acutatum activities with equal MIC values of 3.13 µg/mL. Moreover, diaportheremopholin F (6) and compound 8 displayed antitubercular activity with equal MIC values of 50.0 µg/mL. All tested compounds were non-cytotoxic against MCF-7, NCI-H187, and Vero cells, except those compounds 2 and 5-7 exhibited weak cytotoxicity against both malignant and non-malignant cells with IC50 values in a range of 15.5-115.5 µM.

Frenolicins H and I from the caterpillar-associated Streptomyces sp. TBRC17107.

Two undescribed frenolicins H and I (1 and 2) along with six previously described frenolicin analogues [frenolicins A (3), B (4), UCF76-B (5), E - G (6 - 8)] and two anthraquinones [3,8-dihydroxy-1-propylanthraquinone-2-carboxylic acid (9) and 3,8-dihydroxy-1-propylanthraquinone (10)] were isolated from a longkong bark eating caterpillar-derived Streptomyces sp. TBRC17107. The chemical structures were determined by NMR spectroscopic information and HRESIMS data. Frenolicins H (1) and I (2) showed weak cytotoxicity against malignant and non-malignant cells. Frenolicins A (3) and B (4) showed antimalarial activity against Plasmodium falciparum (IC50 17.4 and 1.37 µM), antibacterial activity against Bacillus cereus and Staphylococcus aureus (MIC 50.0 and 0.20 µg/mL). Only frenolicin B had anti-plant pathogenic fungal activity against Collectotrichum acutatum and Alternaria brassicicola with MIC values of MIC 1.56 and 6.25 µg/mL, respectively. Frenolicins A and G possessed anti-Mycobacterium tuberculosis with equal MICs of 25.0 µg/mL.

Streptomyces telluris sp. nov., a promising terrestrial actinobacterium with antioxidative potentials.

An actinomycete strain, AA8T, which produced a long straight chain of spores (verticillati type), was isolated from the rhizosphere soil of Mangifera indica in Bangkok, Thailand. A polyphasic taxonomic study was carried out to establish the taxonomic position of the strain. Strain AA8T formed a tight taxonomic position in the 16S rRNA gene tree with Streptomyces roseifaciens MBT76T. In contrast, the genome-based taxonomic analysis showed that strain AA8T shared low average nucleotide identity-BLAST (94.1%), the digital DNA-DNA hybridization (58.2%), and the average amino acid identity (93.6%) values with S. roseifaciens MBT76T. Moreover, a combination of physiological and biochemical properties indicated that strain AA8T was distinguished from all Streptomyces species with effectively published names. Strain AA8T, therefore, represents a novel species of Streptomyces, and the name Streptomyces telluris is proposed for the strain. The type strain is AA8T (= TBRC 8483T = NBRC 113461T). The chemical investigation led to the isolation of nine known compounds (compounds 1-9). Among these compounds, compound 7 (3,4-dihydroxybenzaldehyde) possesses strong antioxidant activity equal to ascorbic acid, a powerful antioxidative agent.

Antimalarial and antimicrobial substances isolated from the endophytic actinomycete, Streptomyces aculeolatus MS1-6.

Seven undescribed compounds, including four naphthoquinone terpenoids (aculeolatins A - D), one rare 2-nitropyrrole terpenoid (nitropyrrolin F), and two hydroxamate siderophores (aculeolamides A and B) and one further undescribed compound (2,5,7-trihydroxy-3,6-dimethylnaphthalene-1,4-dione), together with eleven known compounds (arromycin, phenaziterpene A, nitropyrrolin A, heronapyrroles A and B, salaceyin A, 5,7-dihydroxy-2-isopropylchromone, 1-hydroxyphenazine, 1-methoxyphenazine, 1-acetyl-ß-carboline, and N-(2-phenylethyl) acetamide), were isolated from the cultures of the endophytic Streptomyces aculeolatus MS1-6. The structures of the isolated compounds were determined using NMR spectroscopy and corroborated using chemical modification. These compounds exhibited a broad spectrum of biological activities, including antimalarial (IC50 6.03-9.84 µg/mL), antitubercular (MIC 3.13-6.25 µg/mL), anti-plant pathogenic fungal (MIC 25.0-50.0 µg/mL), and antibacterial (MIC 3.03-50 µg/mL) activities; however, they displayed unremarkable cytotoxicity against cancerous (MCF-7 and NCI-H187) and non-cancerous (Vero) cell lines.

Abyssomicin derivatives from the rhizosphere soil actinomycete Microbispora rhizosphaerae sp. nov. TBRC6028.

Three undescribed abyssomicin derivatives, including microbimisin, abyssomicins Z1, and Z2, were isolated from the soil actinomycete Microbispora rhizosphaerae sp. nov. TBRC6028. Chemical structures were determined by NMR spectroscopic data (1H, 13C, COSY, HSQC, HMBC, and NOESY spectra) and the absolute configurations were verified by single-crystal X-ray diffraction analyses together with the ECD spectral data. Microbimisin and abyssomicin Z1 exhibited weak antibacterial activity against Bacillus cereus with MIC values of 25.0 and 50.0 µg/mL without cytotoxicity against MCF-7 and Vero cells at the concentration of 50 µg/mL.

Chromone derivatives, R- and S- taeniolin, from the marine-derived fungus Taeniolella sp. BCC31839.

Two unknown enantiomeric compounds, named (R)- and (S)-taeniolin, along with six known compounds, were isolated from the marine-associated fungus Taeniolella sp. BCC31839. Chemical structures were determined by NMR spectroscopic techniques, and the absolute configurations were confirmed by Mosher application together with CD spectral analyses. Both were inactive for antimicrobial activity against multidrug-resistant malaria parasite (Plasmodium falciparum) and bacteria (Mycobacerium tuberculosis and Bacillus cereus) at maximum tested concentration.

Neuroprotective potential of new chromones isolated from the soil actinomycete Microbispora sp. TBRC6027.

Nine new chromone analogs (1-9) were isolated from the soil actinomycete Microbispora sp. TBRC6027. The chemical structures were determined based upon NMR spectroscopic methods. These compounds were evaluated in vitro by using P19-derived neurons for neuroprotective activity against oxidative stress induced by serum deprivation and showed % viability of neurons at the concentration of 1 ng/mL varied from 43.51% to 52.99% without significant neurotoxicity for P19-derived neurons at the same concentration. Moreover, all tested compounds were inactive for antibacterial activity against both Gram-positive and Gram-negative bacteria and for cytotoxicity against MCF-7 (human breast cancer) and Vero cells at maximum tested concentration 50 µg/mL. However, compounds 4, 6, and 7 displayed weak cytotoxicity against NCI-H187 (human small-cell lung cancer) cells with IC50 in a range of 87.99-91.57 µM.

A novel diterpene agent isolated from Microbispora hainanensis strain CSR-4 and its in vitro and in silico inhibition effects on acetylcholine esterase enzyme.

An actinomycete strain CSR-4 was isolated from the rhizosphere soil of Zingiber montanum. Taxonomic characterization revealed strain CSR-4 was a member of the genus Microbispora. Whole-genome sequence analysis exhibited the highest average nucleotide identity (ANI) value (95.34%) and digital DNA-DNA hybridization (DDH) value (74.7%) between strain CSR-4 and the closest relative M. hainanensis DSM 45428T, which was in line with the assignment to same species. In addition, a new diterpene compound, 2α-hydroxy-8(14), 15-pimaradien-17, 18-dioic acid, and nine known compounds were isolated from the ethyl acetate crude extract of fermentation broth. Interestingly, a new diterpene displayed the suppressive effect on the recombinant human acetylcholinesterase (rhAChE) enzymes (IC50 96.87 ± 2.31 µg/ml). In silico studies based on molecular docking and molecular dynamics (MD) simulations were performed to predict a binding mode of the new compound into the binding pocket of the rhAChE enzyme and revealed that some amino acids in the peripheral anions site (PAS), anionic subsite, oxyanion site and catalytic active site (CAS) of the rhAChE have interacted with the compound. Therefore, our new compound could be proposed as a potential active human AChE inhibitor. Moreover, the new compound can protect significantly the neuron cells (% neuron viability = 88.56 ± 5.19%) from oxidative stress induced by serum deprivation method at 1 ng/ml without both neurotoxicities on murine P19-derived neuron cells and cytotoxicity against Vero cells.

Antibacterial, antitubercular, antimalarial and cytotoxic substances from the endophytic Streptomyces sp. TBRC7642.

Eight previously undescribed naturally-occurring compounds, including abyssomycins Y - Z, methyl aeruginoate, desferri-ferrithocin-4-hydroxyphenethylester, streptomethiocins A - B, furaquinocin I, and streptolactone, along with eleven known compounds were isolated from the endophytic Streptomyces sp. TBRC7642. The chemical structures were determined based on spectroscopic means including 1D, 2D NMR spectroscopy and mass spectrometry. The absolute configurations were assigned by relying on CD spectra and their optical rotations. In addition, the isolated compounds were evaluated for biological activity, such as antimalarial, antitubercular, antibacterial (both Gram-positive and Gram-negative bacteria), as well as for cytotoxicity against MCF-7, NCI-H187, and Vero cells.

Antimicrobial drimane - phthalide derivatives from Hypoxylon fendleri BCC32408.

Fourteen new compounds including thirteen drimane - phthalide derivatives (fendlerals A - C, fendlerins A - D, fendlerols A - B, fendleric acids A - C, fendlerinine G) and one terphenyl derivative (fendleryl E) along with eight known compounds, fendlerinine A, rickenyls C - D, fendleryls C - D, atromentin, tetramethyl atromentin, and (±)-microsphaerophthalide F, were isolated from the wood fungus Hypoxylon fendleri BCC32408. Compared with the prior work, the results indicated the agitation effect on the production of bioactive drimane - phthalides. The chemical structures were determined based upon spectroscopic analyses and the absolute configurations were verified by comparison of the ECD spectral data with the calculated ECD spectra of the related compounds. Compounds 1-3 exhibited antimicrobial activity against Plasmodium falciparum (IC50 4.15-4.39 µM), Colletotrichum capsici (MIC 6.25-12.5 µg/mL), and Bacillus cereus (MIC 1.56-3.13 µg/mL). All tested compounds displayed broad cytotoxicity against cancerous (MCF-7, KB, and NCI-H187) and non-cancerous (Vero) cells.

Antimicrobial substances from the rare actinomycete Nonomuraea rhodomycinica NR4-ASC07T.

Nonomuraea rhodomycinica NR4-ASC07T is a rare actinomycete isolated from soil in Sirindhorn peat swamp forest. The crude extract of its culture broth exhibited antimicrobial and anticancer against diverse human pathogens and cancer cells. The chemical investigation of the crude extract led to the isolation of two new metabolites named nonomuric acid (1) and 3-hydroxy deoxydaunorubicinol aglycone (2), along with two known bioactive compounds [ε-rhodomycinone (3) and 7-deoxy-13-dihydrocarminomycinone (4)]. Compounds 1 and 3 showed antimalarial activity with the half maximal inhibitory concentration (IC50) of 8.00 and 8.88 µg mL-1, respectively. Compound 4 inhibited growth of Mycobacterium tuberculosis and Bacillus cereus at the minimum inhibitory concentrations of 50.0 and 12.50 µg mL-1, respectively. Every compound exhibited cytotoxicity against cancer cells tested at IC50 ≥ 6.34 µg mL-1. These finding are the first report of bioactive metabolites produced by strain NR4-ASC07T, suggesting that rare actinomycetes are yet promising sources for novel drug discovery.

Terphenyl derivatives and drimane - Phathalide/isoindolinones from Hypoxylon fendleri BCC32408.

The genus Hypoxylon, a member of the family Xylariaceae, has been known to produce significant secondary metabolites in terms of chemical diversity. Moreover, the compounds isolated can also be used as chemotaxonomic characters for differentiation among the two sections, which are sect. Annulata and sect. Hypoxylon. In our continuing chemical screening programme for novel compounds, the crude extracts of H. fendleri BCC32408 gave significant chemical profiles in HPLC analyses. Thus, the chemical investigation of these crude extracts was then carried out. The investigation led to the isolation of ten previously undescribed compounds including three terphenylquinones (fendleryls A - C), one terphenyl (fendleryl D), and six novel drimane - phthalide-type lactone/isoindolinones derivatives (fendlerinines A - F) along with seven known compounds (2-O-methylatromentin, rickenyl E, atromentin, rickenyls C - D, (+)-ramulosin, and O-hydroxyphenyl acetic acid). The chemical structures were determined on the basis of spectroscopic analyses, including 1D, 2D NMR and high-resolution mass spectrometry, as well as chemical transformations. In addition, these isolated compounds were assessed for antimicrobial activity including antimalarial (against Plasmodium falciparum, K-1 strain), antifungal (against Candida albicans), antibacterial (against Bacillus cereus) activities. Cytotoxicity against both cancerous (KB, MCF-7, NCI-H187) and non-cancerous (Vero) cells of these compounds were also evaluated.