Search

Three new lavandulylated flavonoids, (2 S ,2'' S )-6-lavandulyl-7,4'-dimethoxy-5,2'-dihydroxylflavanone ( 1 ), (2 S ,2'' S )-6-lavandulyl-5,7,2',4'-tetrahydroxylflavanone ( 2 ), and (2'' S )-5'-lavandulyl-2'-methoxy-2,4,4',6'-tetrahydroxylchalcone ( 3 ), along with seven known compounds 4 - 10 were isolated from culture broth of Streptomyce s sp. G248. Their structures were established by spectroscopic data analysis, including 1D and 2D nuclear magnetic resonance (NMR), and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS). The absolute configurations of 1 - 3 were resolved by comparison of their experimental and calculated electronic circular dichroism spectra. Compounds 1 - 3 exhibited remarkable antimicrobial activity. Whereas, two known compounds 4 and 5 exhibited inhibitory activity against Mycobacterium tuberculosis H37Rv with minimum inhibitory concentration (MIC) values of 6.0 µg/mL and 11.1 µg/mL, respectively., Competing Interests: The authors declare no conflicts of interest

Tuberculosis, caused by Mycobacterium tuberculosis, continues to be a serious public health problem around the world, and it urges the need for development of new antitubercular drugs. An antibiotic producing strain, Streptomyces luridus (MTCC 4402) was earlier isolated from soil by our group. In this work, the phylogenic status was established by 16S rRNA gene sequence analysis. The strain was found to be active against clinically resistant strains. The culture was grown in shake flasks in a medium containing cornsteep liquor, glucose, CaCO(3), soyabean meal and starch. Antibiotic production reached maximum at the end of 72 h. and fermentation profile was obtained. The active compound was extracted into ethyl acetate and was subjected to activity guided purification by column chromatography using silica gel, TLC and HPLC methods. The pure compound eluted at 16.7 min. by gradient elution was subjected to (1)H, (13)C NMR and mass spectral analyses. The acquired data was compared with that of natural products’ data base and found to be a known antibiotic, spiramycin. The purified compound was studied for mutagenic, cytotoxicity, antitubercular activities. It was non mutagenic at the concentration of 1000 μg/mL, non cytotoxic and active as antitubercular agent at a concentration of 64 mg/mL and was comparable to rifampicin.

In this paper, an antimycobacterial component of extracellular metabolites of a gut bacterium Raoultella ornithinolytica from D. veneta earthworms was isolated and its antimycobacterial action was tested using Mycobacterium smegmatis. After incubation with the complex obtained, formation of pores and furrows in cell walls was observed using microscopic techniques. The cells lost their shape, stuck together and formed clusters. Surface-enhanced Raman spectroscopy analysis showed that, after incubation, the complex was attached to the cell walls of the Mycobacterium. Analyses of the component performed with Fourier transform infrared spectroscopy demonstrated high similarity to a bacteriocin nisin, but energy dispersive X-ray spectroscopy analysis revealed differences in the elemental composition of this antimicrobial peptide. The component with antimycobacterial activity was identified using mass spectrometry techniques as a glycolipid-peptide complex. As it exhibits no cytotoxicity on normal human fibroblasts, the glycolipid-peptide complex appears to be a promising compound for investigations of its activity against pathogenic mycobacteria., (© 2015 APMIS. Published by John Wiley & Sons Ltd.)

This study focused on an 80% ethanol:water extract of Galenia africana and Dicerothamnus rhinocerotis in which a phytochemical study revealed the presence of flavonoids as the major secondary plant metabolites. Eleven pure flavonoids viz., (E)-2',4'-dihydroxychalcone 1, (S)-7-hydroxyflavanone 2, (E)-2',4'-dihydroxy-2,3-dihydrochalcone 3, (S)-5,7-dihydroxyflavanone 4, (S)-2',5,7,-trihydroxyflavanone 5, (S)-5,7-dihydroxy-2'-methoxyflavanone 6, 5,7-dihydroxy-4H-chromen-4-one 7, (S)-5-hydroxy-7-methoxyflavanone 8 and (E)-2-hydroxy-3',6'-dimethoxychalcone 9 were isolated from G. africana, while [sakuranetin] (S)-4',5-dihydroxy-7-methoxyflavanone 10 and [eriodictyol-3',7-dimethyl ether] (S)-4',5-dihydroxy-3',7-dimethoxyflavanone 11 were isolated from D. rhinocerotis. Compounds 6 and 9 are new while this is the first reported isolation of 1, 2, 3, 4, 5, 7, 8, 10 and 11 from these plants. All isolated compounds were tested for their antimycobacterial activity against the reference strain Mtb H37Rv. The most active compound, 9, demonstrated a MIC99 of 5 μM against Mtb H37Rv American Type Culture (ATCC) and (ATCC27294), which were also sensitive to Isoniazid (INH) and Rifampicin. The antibacterial activity of 9 might be ascribed to the presence of features such as the α,β-unsaturated ketone and the substitution patterns on the A and B rings.

Exogenous pulmonary surfactant is a potential delivery system for topical medications via the conducting airways. Due to the sensitivity to inactivation of surfactant, mutual interaction with the shipped drug should be evaluated. Little is known about the interactions between surfactant and antimicrobial drugs. The aim of the present study was to evaluate whether biophysical properties of animal-derived surfactants are modified by the bactericidal antibiotic rifampicin. An intracellular activity and a broad antimicrobiotic spectrum toward Gram-negative and Gram-positive bacteria make rifampicin an interesting substance against pulmonary infections. Curosurf® (porcine surfactant from minced lungs) and Survanta® (bovine surfactant extract) were diluted to 2.5-5.0 mg/ml of phospholipids in 0.9 % NaCl and rifampicin (RIF) was added at 1, 5, and 10 % (w/w). Minimum (γ(min)) and maximum (γ(max)) surface tension of a cyclically compressed bubble in the mixture was assessed with a pulsating bubble surfactometer. After 5 min, γ(min) of Survanta at a concentration of 3 mg/ml was significantly increased after addition of 5 and 10 % RIF (both p < 0.001). At 1 % RIF, the γ(min) of Survanta was ≈10 mN/m and this value was not significantly different to that of Survanta alone. The γ(min) of Curosurf at 3 mg/ml was increased with 10 % RIF (p < 0.001), but not with 1 and 5 %. At 5 mg/ml Survanta was inhibited by 10 % RIF (p < 0.05), while γ(min) of Curosurf was low (<5 mN/m) in all mixtures. In conclusion, Curosurf and Survanta interfere with RIF in a concentration-dependent manner. At the appropriate phospholipid concentration, especially porcine-derived surfactant is able to retain good surface activity when mixed with antibiotics.

The n-hexane extract of Lovage root was found to significantly inhibit the growth of both Mycobacterium smegmatis mc²155 and Mycobacterium bovis BCG, and therefore a bioassay-guided isolation strategy was undertaken. (Z)-Ligustilide, (Z)-3-butylidenephthalide, (E)-3-butylidenephthalide, 3-butylphthalide, α-prethapsenol, falcarindiol, levistolide A, psoralen and bergapten were isolated by chromatographic techniques, characterized by NMR spectroscopy and MS, and evaluated for their growth inhibition activity against Mycobacterium tuberculosis H₃₇Rv using the whole-cell phenotypic spot culture growth inhibition assay (SPOTi). Cytotoxicity against RAW 264.7 murine macrophage cells was employed for assessing their degree of selectivity. Falcarindiol was the most potent compound with a minimum inhibitory concentration (MIC) value of 20 mg/L against the virulent H₃₇Rv strain; however, it was found to be cytotoxic with a half-growth inhibitory concentration (GIC₅₀) in the same order of magnitude (SI < 1). Interestingly the sesquiterpene alcohol α-prethapsenol was found to inhibit the growth of the pathogenic mycobacteria with an MIC value of 60 mg/L, being more specific towards mycobacteria than mammalian cells (SI ~ 2). Colony forming unit analysis at different concentrations of this phytochemical showed mycobacteriostatic mode of action., (Copyright © 2012 John Wiley & Sons, Ltd.)

Efflux pumps are one of the well established mechanisms that contribute to antibiotic resistance in bacteria, such as mycobacteria. As a result, the identification of efflux pump inhibitors is an attractive target in antimicrobial therapy. The isolated compounds, three diarylheptanoids, trans,trans-1,7-diphenylhepta-4,6-dien-3-one (1), (5R)-trans-1,7-diphenyl-5-hydroxyhept-6-en-3-one (2), (3S,5S)-trans-1,7-diphenylhept-1-ene-3,5-diol (3) and the flavonoid pinocembrin (4), from Alpinia katsumadai, Zingiberaceae, were examined for their antimycobacterial activity and their synergistic effects with different antibiotics against M. smegmatis mc(2) 155. Furthermore, these compounds were evaluated as potential EtBr efflux inhibitors. Although they showed weak antimycobacterial activities (MIC ≥ 64 mg/L), especially compound 1 revealed a significant activity on the EtBr accumulation and efflux as well as a synergistic effect in combination with rifampicin., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The increased incidence of Multidrug-Resistant Mycobacterium tuberculosis (MDR-MT) requires the search for alternative antimycobacterial drugs. The main aim of this study was to evaluate the dichloromethane extract from Aristolochia brevipes (Rhizoma) and the compounds isolated from this extract against several mycobacterial strains, sensitive, resistant (monoresistant), and clinical isolates (multidrug-resistant), using the alamarBlue™ microassay. The extract was fractionated by column chromatography, yielding the following eight major compounds: (1) 6α-7-dehydro-N-formylnornantenine; (2) E/Z-N-formylnornantenine; (3) 7,9-dimethoxytariacuripyrone; (4) 9-methoxy-tariacuripyrone; (5) aristololactam I; (6) β-sitosterol; (7) stigmasterol; and (8) 3-hydroxy-α-terpineol. The structures of these compounds were elucidated by 1H- and 13C- (1D and 2D) Nuclear Magnetic Resonance (NMR) spectroscopy. This study demonstrates that the dichloromethane extract (rhizome) of A. brevipes possesses strong in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv (Minimum Inhibitory Concentration value [MIC], 12.5 µg/mL). The most active compound against all mycobacterial strains tested was the compound aristolactam I (5), with MIC values ranging between 12.5 and 25 µg/mL. To our knowledge, this the first report of antimycobacterial activity in this plant.

Mycobacterium tuberculosis is responsible for over 8 million cases of tuberculosis (TB) annually. Natural products may play important roles in the chemotherapy of TB. The immunological activity of Davilla elliptica chloroform extract (DECE) was evaluated in vitro by the determination of hydrogen peroxide (H2O2), nitric oxide (NO), and tumor necrosis factor-alpha (TNF-alpha) release in peritoneal macrophages cultures. DECE was also tested for its antimycobacterial activity against M. tuberculosis using the microplate alamar blue assay. DECE (50, 150, 250 microg/ml) stimulated the production of H2O2 (from 1,79 +/- 0,23 to 7,27 +/- 2,54; 15,02 +/- 2,86; 20,5 +/- 2,1 nmols) (means +/- SD), NO (from 2,64 +/- 1,02 to 25,59 +/- 2,29; 26,68 +/- 2,41; 29,45 +/- 5,87 micromols) (means +/- SD) and TNF-alpha (from 2,44 +/- 1,46 to 30,37 +/- 8,13; 38,68 +/- 1,59; 41,6 +/- 0,90 units/ml) (means +/- SD) in a dose-dependent manner and also showed a promising antimycobacterial activity with a minimum inhibitory concentration of 62,5 microg/ml. This plant may have therapeutic potential in the immunological and microbiological control of TB.

Chemical investigation of the cytotoxic and anti-tuberculosis active butanone extract obtained from the growth media of the marine-derived fungus Beauveria felina led to the isolation of two new destruxins, [beta-Me-Pro] destruxin E chlorohydrin (1) and pseudodestruxin C (3), along with five known cyclic depsipeptides. The structures of the new destruxin derivatives were established by analysis of spectroscopic data, while the absolute configuration of the common amino acid residues was established by Marfey's analysis. The absolute configuration of the 2(R),4(S)-5-chloro-2,4-dihydroxypentanoic acid residue in 1 could be established by application of a J-based configuration method followed by derivatization with R-MPA-Cl and NMR analysis.

Optimal fermentation conditions for enniatin production using the entomopathogenic fungus Verticillium hemipterigenum BCC 1449 have been investigated. Among various liquid media tested, highest efficiency of enniatin production was achieved by fermentation in yeast extract sucrose. Application of this condition to large-scale fermentation resulted in the isolation of three new analogs, O1, O2 and O3, which are closely related isomers that were characterized as an inseparable mixture, along with seven known enniatins.

The tuberactinomycin antibiotics are essential components in the drug arsenal against Mycobacterium tuberculosis infections and are specifically used for the treatment of multidrug-resistant tuberculosis. These antibiotics are also being investigated for their targeting of the catalytic RNAs involved in viral replication and for the treatment of bacterial infections caused by methicillin-resistant Staphylococcus aureus strains and vancomycin-resistant enterococci. We report on the isolation, sequencing, and annotation of the biosynthetic gene cluster for one member of this antibiotic family, viomycin, from Streptomyces sp. strain ATCC 11861. This is the first gene cluster for a member of the tuberactinomycin family of antibiotics sequenced, and the information gained can be extrapolated to all members of this family. The gene cluster covers 36.3 kb of DNA and encodes 20 open reading frames that we propose are involved in the biosynthesis, regulation, export, and activation of viomycin, in addition to self-resistance to the antibiotic. These results enable us to predict the metabolic logic of tuberactinomycin production and begin steps toward the combinatorial biosynthesis of these antibiotics to complement existing chemical modification techniques to produce novel tuberactinomycin derivatives.

Two new pimarane diterpenes, diaportheins A (1) and B (2), were isolated from a culture broth of the fungus Diaporthe sp. BCC 6140. Diaporthein B (2) strongly inhibited the growth of Mycobacterium tuberculosis with the MIC value of 3.1 microg/mL, while diaporthein A (1) showed only mild activity (MIC value of 200 microg/mL).

Rifampicin was absorbed onto gelatin-sealed (Gelsoft and Unigraft) or collagen-sealed (Hemashield) vascular grafts by soaking for 15 min in a 1000 mg/L solution. Bound drug was then eluted from the grafts by incubation in phosphate buffered saline (PBS) at 37 degrees C and at timed intervals the concentration of rifampicin remaining in the grafts was determined. Although all three grafts contained high concentrations of rifampicin immediately after absorption of drug, rifampicin concentrations rapidly fell during elution with PBS to approximately 1.25 mg/kg of graft after 5 h incubation in PBS, indicating that most of the rifampicin absorbed to the grafts was only loosely bound. However, once this loosely bound fraction had been removed there was a much slower elution of the remaining rifampicin from the grafts, suggesting a second and much more tightly bound fraction. The tightly bound fraction eluted with an apparent half-life of 47-76 h, depending on the graft, and extrapolation back to time zero from this phase suggests that only a very small amount of the rifampicin is tightly bound to the graft after initial soaking (0.6-1.3 mg/kg).

A study of the antimicrobial compounds from Moneses uniflora resulted in the isolation of a novel compound, 8-chloro-2,7-dimethyl-1,4-naphthoquinone (8-chlorochimaphilin) (1), together with chimaphilin (2) and 3-hydroxychimaphilin (3) as the antimicrobial components. 2,7-Dimethyl-1,3-dihydroxynaphthyl 4-O-alpha-L-rhamnopyranoside (4) and 2,7-dimethoxy-1,4,8-trihydroxynaphthalene (6) were also isolated and identified.

Tuberactinamine N, the cyclic peptide moiety of tuberactinomycin N, was obtained in a crystalline state through liberation of gamma-hydroxy-beta-lysine from tuberactinomycin N by acid treatment. Tuberactinamine N possesses an intramolecular hydrogen bond in its molecule and showed antibacterial activities comparable to those of the original antibiotics. Conversion of tuberactinomycin N to O was achieved through coupling of diacyl-beta-lysine with tuberactinamine N followed by removal of the protecting groups.