Modest Antimicrobial Activity Research Articles

Evaluation of Antioxidant , Antimicrobial and Cytotoxicity of Alcea Kurdica Alef

The purpose of this study is to evaluate the aqueous extract of Alcea kurdica Alef for antioxidant and antimicrobial activity as well as potential toxicity. Antioxidant activities were evaluated using 1,1-diphenyl-2- picrylhydrazyl (DPPH) free radical scavenging and Ferric Reducing Antioxidant Power (FRAP) reducing capacity assays as well as total phenolic compounds (TPC). Antimicrobial activity was assessed against some Gram-positive and Gram-negative bacteria, yeasts and filamentous fungi using the agar dilution method. The plant extract was also assessed for in-vitro toxicity using the Promega Cell Titer 96 AQueous Non-Radioactive Cell Proliferation (MTS) assay. The aqueous extract of A. kurdica demonstrated potent free radical scavenging activity of 64% ± 1.64% and ferric reduction capacity of 2955.0 ± 0.04 mmol/g, as well as having 88.0 ± 0.002 mg gallic acid equivalents /gram plant extract. The aqueous extract of A. kurdica had modest antimicrobial activity against most tested microorganisms. Moreover, the plant extract did not have any toxic effects on human lung fibroblasts. Based on these findings, we conclude that A. kurdica may be utilized to prevent the growth of some microorganisms. The plant constituents behind these effects are the antioxidants and phenols. Further studies are needed to evaluate the therapeutic utility of A. kurdica extracts as antimicrobial agents.

Enhanced cellular uptake by “pharmaceutically oriented devices” of new simplified analogs of Linezolid with antimicrobial activity

The aim of the present study was to enhance cellular uptake of simplified analogs of Linezolid by their incorporation into suitable delivery devices in order to improve the antimicrobial activity of these novel synthesized oxazolidin-2-one derivatives. The oxazolidin-2-one derivatives were synthesized by developing a rather simple one-pot reaction starting from oxiranylmethanol and several primary amines. Three delivery devices were prepared by following different synthetic approaches, such as single-step free radical grafting, precipitation polymerization and nano-emulsion. Finally, the antimicrobial activity of the novel synthesized compounds, without any vehicle and after their incorporation into the delivery devices, was evaluated against Escherichia coli and Saccharomyces cerevisiae by performing time-kill analyses. The synthesized oxazolidinones exhibited modest antimicrobial activity against E. coli and S. cerevisiae (MIC 16 μg/mL). A good activity was, instead, highlighted after their incorporation into the prepared delivery devices (lecithin-based nano-emulsion, poly(N-vinyl-pyrrolidone)-methacrylic acid grafted copolymer and spherical polymeric nanoparticles) (MIC≤4 μg/mL). The incorporation into suitable vehicles, indeed, reduced by 4 times the normal MICs of the newly synthesized oxazolilidin-2-ones and represents an effective strategy to overcome cellular penetration constraints.

Ability of Innate Defence Regulator Peptides IDR-1002, IDR-HH2 and IDR-1018 to Protect against Mycobacterium tuberculosis Infections in Animal Models

Tuberculosis is an ongoing threat to global health, especially with the emergence of multi drug-resistant (MDR) and extremely drug-resistant strains that are motivating the search for new treatment strategies. One potential strategy is immunotherapy using Innate Defence Regulator (IDR) peptides that selectively modulate innate immunity, enhancing chemokine induction and cell recruitment while suppressing potentially harmful inflammatory responses. IDR peptides possess only modest antimicrobial activity but have profound immunomodulatory functions that appear to be influential in resolving animal model infections. The IDR peptides HH2, 1018 and 1002 were tested for their activity against two M. tuberculosis strains, one drug-sensitive and the other MDR in both in vitro and in vivo models. All peptides showed no cytotoxic activity and only modest direct antimicrobial activity versus M. tuberculosis (MIC of 15–30 µg/ml). Nevertheless peptides HH2 and 1018 reduced bacillary loads in animal models with both the virulent drug susceptible H37Rv strain and an MDR isolate and, especially 1018 led to a considerable reduction in lung inflammation as revealed by decreased pneumonia. These results indicate that IDR peptides have potential as a novel immunotherapy against TB.

Novel Dibenzo[b,e]oxepinones from the Freshwater-Derived Fungus Chaetomium sp. YMF 1.02105

Six new dibenzo[b,e]oxepinone metabolites, chaetones A-F (1-6), as well as three known compounds, 1-hydroxy-6-methyl-8-hydroxymethylxanthone (7), citreorosein (8), and emodin (9), were obtained from a freshwater-derived fungal strain Chaetomium sp. YMF 1.02105. Their structures were established on the basis of extensive spectroscopic data analysis and comparison with spectroscopic data reported. Compounds 1-6 are further additions to the small group of dibenzo[b,e]oxepinones represented by arugosins A-H. Compounds 1-7 were tested for their cytotoxic activities against A549, Raji, HepG2, MCF-7, and HL-60 cell lines. The results showed that compound 3 had significant cytotoxicity with IC50 values of 1.2, 1.8, 1.9, 2.3, and 1.6 µg/mL, respectively, against the five cancer cell lines. All compounds showed modest antimicrobial activity against Staphylococcus aureus (ATCC 6538) in standard disk assays.

Precursor-centric genome-mining approach for lasso peptide discovery

Lasso peptides are a class of ribosomally synthesized posttranslationally modified natural products found in bacteria. Currently known lasso peptides have a diverse set of pharmacologically relevant activities, including inhibition of bacterial growth, receptor antagonism, and enzyme inhibition. The biosynthesis of lasso peptides is specified by a cluster of three genes encoding a precursor protein and two enzymes. Here we develop a unique genome-mining algorithm to identify lasso peptide gene clusters in prokaryotes. Our approach involves pattern matching to a small number of conserved amino acids in precursor proteins, and thus allows for a more global survey of lasso peptide gene clusters than does homology-based genome mining. Of more than 3,000 currently sequenced prokaryotic genomes, we found 76 organisms that are putative lasso peptide producers. These organisms span nine bacterial phyla and an archaeal phylum. To provide validation of the genome-mining method, we focused on a single lasso peptide predicted to be produced by the freshwater bacterium Asticcacaulis excentricus. Heterologous expression of an engineered, minimal gene cluster in Escherichia coli led to the production of a unique lasso peptide, astexin-1. At 23 aa, astexin-1 is the largest lasso peptide isolated to date. It is also highly polar, in contrast to many lasso peptides that are primarily hydrophobic. Astexin-1 has modest antimicrobial activity against its phylogenetic relative Caulobacter crescentus. The solution structure of astexin-1 was determined revealing a unique topology that is stabilized by hydrogen bonding between segments of the peptide.

Simplified platensimycin analogues as antibacterial agents

A series of substituted 2-hydroxybenzoic acid derivatives were synthesized as simplified analogues of platensimycin. The final compounds were evaluated against the Gram-positive bacteria, methicillin-resistant Staphylococcus aureus. Analogues that possessed polycyclic groups directly attached to the substituted benzoic acid were able to demonstrate modest antimicrobial activity.

Heronamycin A: a new benzothiazine ansamycin from an Australian marine-derived Streptomyces sp.

Chemical analysis of a marine-derived Streptomyces sp. (CMB-M0392) isolated from sediment collected off Heron Island, Queensland, Australia, yielded a new benzothiazine ansamycin, heronamycin A. The absolute stereostructure of heronamycin A was determined by detailed spectroscopic analysis and X-ray crystallography. Heronamycin A exhibited modest antimicrobial activity against Bacillus subtilis strains ATCC 6051 and 6633 (IC50=18 and 14μM, respectively).

α-Pyrones and Diketopiperazine Derivatives from the Marine-Derived Actinomycete Nocardiopsis dassonvillei HR10-5

Three new α-pyrones, nocapyrones E-G (1-3), and three new diketopiperazine derivatives, nocazines A-C (4-6), together with a new oxazoline compound, nocazoline A (7), were isolated from the marine-derived actinomycete Nocardiopsis dassonvillei HR10-5. The new structures of 1-7 were determined by spectroscopic analysis, X-ray single-crystal diffraction, CD spectra, and modified Mosher and Marfey methods. Compounds 1-3 showed modest antimicrobial activity against Bacillus subtilis with MIC values of 26, 14, and 12 μM, respectively.

Maklamicin, an Antibacterial Polyketide from an Endophytic Micromonospora sp.

A new spirotetronate-class polyketide, maklamicin (1), was isolated from the culture extract of an endophytic actinomycete of the genus Micromonospora. The structure and relative configuration of 1 were elucidated by interpretation of NMR and other spectroscopic data, and the absolute configuration was determined using the modified Mosher method. Maklamicin (1) showed strong to modest antimicrobial activity against Gram-positive bacteria.

Selectivity of Inhibition of N-Succinyl-l,l-Diaminopimelic Acid Desuccinylasein Bacteria: The product of dapE-gene Is Not the Target ofl-Captopril Antimicrobial Activity

The emergence of bacterial strains that are resistant to virtually all currently available antibiotics underscores the importance of developing new antimicrobial compounds. N-succinyl-l,l-diaminopimelic acid desuccinylase (DapE) is a metallohydrolase involved in the meso-diaminopimelate (mDAP)/lysine biosynthetic pathway necessary for lysine biosynthesis and for building the peptidoglycan cell wall. Because DapE is essential for Gram-negative and some Gram-positive bacteria, DapE has been proposed as a good target for antibiotic development. Recently, l-captopril has been suggested as a lead compound for inhibition of DapE, although its selectivity for this enzyme target in bacteria remains unclear (Gillner et al. (2009)). Here, we tested the selectivity of l-captopril against DapE in bacteria. Since DapE knockout strains of gram-negative bacteria are viable upon chemical supplementation with mDAP, we reasoned that the antimicrobial activity of compounds targeting DapE should be abolished in mDAP-containing media. Although l-captopril had modest antimicrobial activity in Escherichia coli and in Salmonella enterica, to our surprise, inhibition of bacterial growth was independent both of mDAP supplementation and DapE over-expression. We conclude that DapE is not the main target of l-captopril inhibition in these bacteria. The methods implemented here will be useful for screening DapE-selective antimicrobial compounds directly in bacterial cultures.

In Vitro Activity of Fidaxomicin (OPT-80) Tested against Contemporary Clinical Isolates of Staphylococcus spp. and Enterococcus spp

<i>In Vitro</i> Activity of Fidaxomicin (OPT-80) Tested against Contemporary Clinical Isolates of <i>Staphylococcus</i> spp. and <i>Enterococcus</i> spp

(R)-(-)-carvone and (1R, 4R)-trans-(+)-dihydrocarvone from poiretia latifolia vogel

The essential oils of Poiretia latifolia Vogel, native and cultivated leaves (Samples A and B, respectively) and native flowers (sample C), were obtained by hydrodistillation and analyzed by GC, GC/MS and chiral phase gas chromatography (CPGC). Twenty-four compounds were identified, representing 99.25, 99.26 and 99.23% of the oils, respectively. The major constituents of the oils were the monoterpenes (S)-(-)-limonene (16.05, 27.60, 15.60%, respectively), (1R, 4R)-trans-(+)-dihydrocarvone (18.05, 0.66 and 77.80%, respectively) and (R)-(-)-carvone (61.05, 64.20 and 4.50%, respectively). The essential oils were evaluated against some strains of Gram (+) and Gram (-) bacteria, and yeast, but displayed only modest antimicrobial activity.

Antimicrobial Triterpenoids from Vladimiria muliensis

A new triterpenoid with a rearranged ursane skeleton, 3beta-acetoxyl-11alpha-methoxybauer-8-en-7alpha-ol ( 1), two new ursane triterpenoids, 1alpha,5alpha-dioxy-11alpha-hydroxyurs-12-en-3-one ( 2) and urs-3beta,13alpha,18beta-triol ( 3), together with three known ursane triterpenoids ( 4- 6) were isolated from the rhizome of Vladimiria muliensis. Their structures were elucidated on the basis of spectroscopic methods (IR, EIMS, HRESIMS, 1D and 2D NMR, and X-ray crystallography diffraction). Compounds 2 and 4 exhibited modest antimicrobial activity against Escherichia coli, Candida albicans, Pseudomonas aeruginosa, Enterococcus faecalis, Bacillus cereus, and Staphylococcus aureus.

Alachalasins A–G, new cytochalasins from the fungus Stachybotrys charatum

Alachalasins A–G ( 1– 7), seven new cytochalasin-type of metabolites, have been isolated from cultures of an isolate of Stachybotrys charatum. The structures of these compounds were determined mainly by analysis of their NMR spectroscopic data, and the absolute configuration of 1 was assigned by application of the modified Mosher method. Alachalasin A ( 1) displayed inhibitory effect on HIV-1 LAI replication in C8166 cells with an EC 50 of 8.01 μM; alachalasins D ( 4) and G ( 7) showed modest antimicrobial activity.

Bioactive p-Terphenyl Derivatives from a Cordyceps-Colonizing Isolate of Gliocladium sp.

Gliocladinins A (1) and B (2), two new p-terphenyl derivatives, have been isolated from solid cultures of an isolate of Gliocladium sp. that colonizes Cordyceps sinensis. The structures of these compounds were determined mainly by analysis of their NMR spectroscopic data. In standard disk assays, compounds 1 and 2 showed modest antimicrobial activity against Staphylococcus aureus (ATCC 6538). In addition, these compounds displayed inhibitory effects on the growth of two human tumor cell lines, HeLa and HCT116.

Epicoccins A–D, Epipolythiodioxopiperazines from a Cordyceps-Colonizing Isolate of Epicoccum nigrum

Epicoccins A-D (1-4), four unique epipolythiodioxopiperazines possessing unusual sulfur bridges, have been isolated from cultures of a Cordyceps-colonizing isolate of Epicoccum nigrum. The structures of these compounds were determined mainly by analysis of their NMR spectroscopic data. The relative and absolute configuration of epicoccin A (1) was established by single-crystal X-ray diffraction analysis. Epicoccin A (1) showed modest antimicrobial activity.

Cathelicidins and functional analogues as antisepsis molecules

The emergence of antibiotic-resistant bacteria together with the limited success of sepsis therapeutics has lead to an urgent need for the development of alternative strategies for the treatment of systemic inflammatory response syndrome and related disorders. Immunomodulatory compounds that do not target the pathogen directly (therefore limiting the development of pathogen resistance), and target multiple inflammatory mediators, are attractive candidates as novel therapeutics. Cationic host defence peptides such as cathelicidins have been demonstrated to be selectively immunomodulatory in that they can confer anti-infective immunity and modulate the inflammatory cascade through multiple points of intervention. The human cathelicidin LL-37, for example, has modest direct antimicrobial activity under physiological conditions, but has been demonstrated to have potent antiendotoxin activity in animal models, as well as the ability to resolve certain bacterial infections. A novel synthetic immunomodulatory peptide, IDR-1, built on this same theme has no direct antimicrobial activity, but is effective in restricting many types of infection, while limiting pro-inflammatory responses. The ability of these peptides to selectively suppress harmful pro-inflammatory responses, while maintaining beneficial infection-fighting components of host innate defences makes them a good model for antisepsis therapies that merit further investigation.

Interaction and Cellular Localization of the Human Host Defense Peptide LL-37 with Lung Epithelial Cells

LL-37 is a human cationic host defense peptide that is an essential component of innate immunity. In addition to its modest antimicrobial activity, LL-37 affects the gene expression and behavior of effector cells involved in the innate immune response, although its mode of interaction with eukaryotic cells remains unclear. The interaction of LL-37 with epithelial cells was characterized in tissue culture by using biotinylated LL-37 and confocal microscopy. It was demonstrated that LL-37 was actively taken up into A549 epithelial cells and eventually localized to the perinuclear region. Specific inhibitors were used to demonstrate that the uptake process was not mediated by actin but required elements normally involved in endocytosis and that trafficking to the perinuclear region was dependent on microtubules. By using nonlinear regression analysis, it was revealed that A549 epithelial cells have two receptors for LL-37B, with high and low affinity for LL-37, respectively. These results indicate the mode of interaction of LL-37 with epithelial cells and further our understanding of its role in modulating the innate immune response.

Activity of a broad-spectrum cephalosporin (Ro 48-8391) alone and in combination with two novel β-lactamase inhibitors (Ro 48-5545 and Ro 48-8724)

The susceptibility of a group of β-lactamase–producing and drug-resistant Gram-positive and Gram-negative organisms was tested against a novel cephalosporin (Ro 48-8391) alone and in combination with two bridged carbacephem β-lactamase inhibitors (Ro 48-5545 or Ro 48-8724) and compared with that of ceftriaxone, ceftazidime, and cefepime (representative “third- and fourth-generation” cephalosporins), imipenem, and a combination of piperacillin and tazobactam. Five hundred and one selected clinical isolates were tested using the reference broth microdilution method (National Committee for Clinical Laboratory Standards). Ro 48-8391 has a spectrum of activity and potency most similar to ceftriaxone but with improved activity against Gram-positive species. The two β-lactamase inhibitors, Ro 48-5545 and Ro 48-8724, have modest antimicrobial activity. When combined with Ro 48-8391, the β-lactamase inhibitor Ro 48-8724 was superior to the combination of Ro 48-8391 and Ro 48-5545 in spectrum and enzyme inhibition against extended spectrum β-lactamase enzyme-producing Escherichia coli and Klebsiella pneumoniae, and against Enterobacteriaceae with “stably derepressed” Bush-Jacoby-Medeiros gr. 1 enzymes (ceftazidime-resistant Enterobacter and Citrobacter). Ro 48-5545 and Ro 48-8724 appear to be promising β-lactamase inhibitors with potential application against chromosomal- and plasmid-mediated enzymes. Ro 48-8391, although superior to some currently available “third-generation” cephems, was not a well-matched active codrug because of limited activity against several commonly isolated species of clinically important bacteria. Further efforts are necessary to find a penicillin or cephem with activity more complementary to that of the tested β-lactamase inhibitors and the Ro 48-8391 compound could be focused for therapeutic use in serious streptococcal infections.

Labdane diterpenes from the marine pulmonate gastropod Trimusculus peruvianus

The marine gastropod mollusk Trimusculus peruvianus collected on the coast of Central Chile yielded four new labdane metabolites. The structural elucidation of all compounds was accomplished by spectral analysis. One diterpenoid showed modest antimicrobial activity. Key words: Trimusculus peruvianus, labdanes, marine mollusk.