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Antiparasitic activity of flavonoids and isoflavones against Cryptosporidium parvum and Encephalitozoon intestinalis.

Flavonoids, polyphenolic compounds found in plants, have demonstrated activity against several parasites and can augment the efficacy of other drugs by either increasing the uptake or decreasing the efflux of these drugs. We evaluated 11 of these compounds alone or in combination in order to test the hypothesis that flavonoids are effective against Cryptosporidium parvum and Encephalitozoon intestinalis. Using in vitro cell culture assays, HCT-8 cells or E6 cells were infected with C. parvum and E. intestinalis, respectively, and treated with compounds at doses ranging from 1 to 200 microM. We found that six compounds were active against C. parvum. Naringenin and genistein had the greatest activities with EC(50) of 15 and 25 microM, respectively. Two compounds, quercetin and apigenin, had activity against E. intestinalis at EC(50) of 15 and 50 microM, respectively. The EC(50) of trifluralin, a dinitroaniline compound, was decreased significantly when combined with genistein in an in vitro assay, suggesting that compounds may be used alone on in combination with other moderately active drugs to increase efficacy. In addition, induction of apoptosis by these compounds was studied but not observed to be a significant mechanism of action.

Animals↗

Antibacterial, antiprotozoal and antioxidant activity of five plants used in Izabal for infectious diseases.

Methanol and aqueous extracts from fi ve plant species, used in traditional medicine in Guatemala for the treatment of microbial infections, were tested in vitro for their ability to scavenge DPPH, OH(.) and O(2) (-) radicals and to inhibit lipoperoxidation (LPO) in order to establish a relationship between their antioxidant activities and their effects against infectious agents. Acalypha guatemalensis, Ocimum micranthum and Smilax spinosa possessed a significant activity against both the three free radicals assayed and LPO; Guazuma ulmifolia showed effects against DPPH and OH(.). Piper auritum showed no activity. These extracts were also evaluated for antibacterial and antiprotozoal activities. A. guatemalensis showed activity against Pseudomonas aeruginosa; S. spinosa was active against Salmonella typhi, and A. guatemalensis, and S. spinosa against Trypanosoma cruzi or Leishmania spp.

Animals↗

Anti-infective potential of natural products: how to develop a stronger in vitro 'proof-of-concept'.

Natural products, either as pure compounds or as standardized plant extracts, provide unlimited opportunities for new drug leads because of the unmatched availability of chemical diversity. To secure this, a number of pivotal quality standards need to be set at the level of extract processing and primary evaluation in pharmacological screening models. This review provides a number of recommendations that will help to define a more sound 'proof-of-concept' for antibacterial, antifungal, antiviral and antiparasitic potential in natural products. An integrated panel of pathogens is proposed for antimicrobial profiling, using accessible standard in vitro experimental procedures, endpoint parameters and efficacy criteria. Primary requirements include: (1) use of reference strains or fully characterized clinical isolates, (2) in vitro models on the whole organism and if possible cell-based, (3) evaluation of selectivity by parallel cytotoxicity testing and/or integrated profiling against unrelated micro-organisms, (4) adequately broad dose range, enabling dose-response curves, (5) stringent endpoint criteria with IC(50)-values generally below 100microug/ml for extracts and below 25microM for pure compounds, (6) proper preparation, storage and in-test processing of extracts, (7) inclusion of appropriate controls in each in vitro test replicate (blanks, infected and reference controls) and (8) follow-up of in vitro activity ('hit'-status) in matching animal models ('lead'-status).

Anti-Infective Agents↗

Antimicrobial activity of Cassia alata.

The methanol extracts of leaves, flowers, stem and root barks of Cassia alata showed a broad spectrum of antibacterial activity. The activity was increased on fractionation (petrol, dichloromethane, ethyl acetate), the dichloromethane fraction of the flower extract being the most effective. No activity was shown against tested moulds.

Animals↗

Antimicrobial activity of Clematis papuasica and Nauclea obversifolia.

The methanol extracts of Clematis papuasica leaves and stem bark and of Nauclea obversifolia leaves, stem and root barks showed awide spectrum of antibacterial activity which was increased on fractionation (petrol, dichloromethane, ethyl acetate), the ethyl acetate fractions being in all cases the most effective. None of the extractives was active against tested moulds.

Animals↗

Anti-microbial activity of Bidens pilosa, Bischofia javanica, Elmerillia papuana and Sigesbekia orientalis.

The ethanol extracts of Bidens pilosa (whole plant), Bischofia javanica (leaves), Elmerillia papuana (root bark) and Sigesbekia orientalis (whole plant) were partitioned (petrol, dichloromethane, ethyl acetate). The crude ethanolic extracts and all the obtained fractions showed a broad spectrum of antibacterial activity, the ethyl acetate fractions and the petrol fraction of E. papuana being the most effective. No activity was observed against the tested moulds.

Animals↗

Antimicrobial activity of Lithocarpus celebicus.

The methanol extracts of leaves, stem and root barks of Lithocarpus celebicus showed a broad spectrum of antibacterial activity which was increased on fractionation (petrol, dichloromethane, ethylacetate), particularly in the ethyl acetate fraction of the stem bark and petrol fraction of the root bark. None of the extractives was active against tested moulds.

Animals↗

Bioactive alkyl phenols and embelin from Oxalis erythrorhiza.

The benzoquinone embelin and four alkyl phenols were isolated from an Argentinean collection of Oxalis erythrorhiza. 3-Heptadecyl-5-methoxy-phenol is reported for the first time. The structures were determined by spectroscopic methods. Embelin presented inhibitory effect on methicillin-resistant Staphylococcus aureus, Escherichia coli and the dermatophytic fungi Epidermophyton floccosum, Microsporum canis, Microsporum gypseum, Trichophyton mentagrophytes and Trichophyton rubrum with MICs ranging between 50 and 100 microg/ml. Furthermore, embelin was active against Trypanosoma cruzi trypomastigotes with 100% lysis at 100 microg/ml and cytotoxicity below the trypanocidal concentration. The new alkyl phenol 3-heptadecyl-5-methoxy-phenol was active towards Leishmania amazonensis and Leishmania donovani promastigotes with 100% lysis at 100 microg/ml. The cytotoxicity (IC50) of embelin and the new alkyl phenol on human lung fibroblasts were 739 and 366 microM, respectively. The plant is used to treat heart complains, a symptomatology related to Chagas' disease which is endemic in the San Juan Province, Argentine.

Anti-Bacterial Agents↗

Antiviral and antiplasmodial spirodihydrobenzofuran terpenes from the fungus Stachybotrys nephrospora.

Two known spirodihydrobenzofuran terpenes (1 and 2) were isolated from a mycelium extract of the fungus Stachybotrys nephrospora BCC 3900. Compound 1 (Mer-NF5003F or stachybotrydial) exhibited potent antiviral activity (the IC50 value of 4.32 microg/mL) comparable to the standard drug, acyclovir, while compound 2 was inactive against the HSV-1 virus. Both 1 and 2 possessed antiplasmodial activity (IC50 values of 0.85 and 0.15 microg/mL for 1 and 2, respectively), and were not toxic towards the Vero cell line. A regiospecific conversion of the dialdehyde 1 to the lactone 2 proceeded simply under acidic conditions.

Animals↗

Pharmacological activities of crude acetone extract and purified constituents of Salvia moorcraftiana Wall.

The crude acetone extract of aerial parts of Salvia moorcraftiana Wall. was screened for various biological activities including Lemna bioassay, antifungal, antibacterial, leishmanicidal, insecticidal activities and brine shrimp cytotoxicity. It was found to possess strong phytotoxic activity against Lemna aequinoctials Welve. and moderate antifungal activity against animal and plant pathogens. The purified chemical constituents were tested for enzyme inhibition activity. Two constituents (compounds 3 and 8) were found to be effective inhibitors of alpha-glucosidase.

Animals↗

Effects of acyl versus aminoacyl conjugation on the properties of antimicrobial peptides.

To investigate the importance of increased hydrophobicity at the amino end of antimicrobial peptides, a dermaseptin derivative was used as a template for a systematic acylation study. Through a gradual increase of the acyl moiety chain length, hydrophobicity was monitored and further modulated by acyl conversion to aminoacyl. The chain lengths of the acyl derivatives correlated with a gradual increase in the peptide's global hydrophobicity and stabilization of its helical structure. The effect on cytolytic properties, however, fluctuated for different cells. Whereas acylation gradually enhanced hemolysis of human red blood cells and antiprotozoan activity against Leishmania major, bacteria displayed a more complex behavior. The gram-positive organism Staphylococcus aureus was most sensitive to intermediate acyl chains, while longer acyls gradually led to a total loss of activity. All acyl derivatives were detrimental to activity against Escherichia coli, namely, but not solely, because of peptide aggregation. Although aminoacyl derivatives behaved essentially similarly to the nonaminated acyls, they displayed reduced hydrophobicity, and consequently, the long-chain acyls enhanced activity against all microorganisms (e.g., by up to 12-fold for the aminolauryl derivative) but were significantly less hemolytic than their acyl counterparts. Acylation also enhanced bactericidal kinetics and peptide resistance to plasma proteases. The similarities and differences upon acylation of MSI-78 and LL37 are presented and discussed. Overall, the data suggest an approach that can be used to enhance the potencies of acylated short antimicrobial peptides by preventing hydrophobic interactions that lead to self-assembly in solution and, thus, to inefficacy against cell wall-containing target cells.

Acylation↗

Broad spectrum antimicrobial activity of a new multi-purpose disinfecting solution.

PURPOSE: There has been increasing awareness of the need for more powerful contact lens disinfectants, ideally having low toxicity and allergenicity to ocular tissue. Opti-Free Express with ALDOX Multi-Purpose Disinfecting Solution (MPDS) was recently marketed as a new multi-purpose disinfecting solution for soft contact lenses. MPDS contains two antimicrobial agents, polyquaternium-1 and myristamidopropyl dimethylamine, to broaden the range of antimicrobial activity. The purpose of this study was to evaluate the antimicrobial activity of MPDS against microorganisms that have been reported as contact lens and lens case contaminants and causative agents of microbial keratitis. METHODS: MPDS was challenged with high numbers of gram-positive and gram-negative bacteria, yeast, mold, and Acanthamoeba. Several lots of product were challenged with at least three separate inocula of each isolate. After exposure to the disinfecting solution, a sample was removed from the product and plated for survivors by suitable recovery methods. The plates were incubated and the number of survivors was enumerated. RESULTS: The results showed that MPDS was bactericidal, fungicidal and amoebicidal against an extensive variety of environmental contaminants of lens care accessories and ocular pathogens. MPDS was capable of killing a broad spectrum of microorganisms. The log reduction exceeded the primary criteria for disinfecting products and produced a notable reduction of other clinical and environmental isolates as well. CONCLUSIONS: Opti-Free Express MPDS contains antimicrobial agents that can kill an extensive spectrum of many different types of microorganisms that may contaminate contact lenses and solutions.

Acanthamoeba↗

Antimicrobic and anthelmintic resistance.

Antimicrobial and anthelmintic resistance are growing issues for the equine practitioner. The development of antimicrobial or anthelmintic resistance is a source of significant concern because of increased frequency of treatment failures and increased treatment costs. In addition, antimicrobial resistance may have important consequences for public health. Only through judicious use can the efficacy of antimicrobials and anthelmintics be prolonged. This article discusses the development of resistance and suggestions for control.

Animals↗

Munumbicins E-4 and E-5: novel broad-spectrum antibiotics from Streptomyces NRRL 3052.

Streptomyces NRRL 30562 was originally isolated as an endophyte from Kennedia nigriscans, snakevine, in the Northern Territory of Australia. This plant has been used for centuries by Aboriginal peoples to treat open bleeding wounds to prevent sepsis. A solvent extract of the crude fluid from cultures of this endophyte possesses wide-spectrum antibiotic activity. Some of the bioactivity is associated with the appearance of actinomycins X2, D, and Xobeta, the first two of which had been previously designated munumbicins A and B, respectively. Other novel compounds bearing wide-spectrum antibiotic activity are also produced by Streptomyces NRRL 30562, and these are designated munumbicins E-4 and E-5. Mass spectrometric analyses of these peptide antibiotics show that they have identical masses (1445.00) but different retention times on HPLC. Both compounds showed activity against gram-positive and gram-negative bacteria. The plant pathogenic fungus, Pythium ultimum is sensitive to both munumbicins at 5.0 microg mL(-1) The malarial parasite, Plasmodium falciparum has IC50 values of 0.50+/-0.08 and 0.87+/-0.0.26 microg mL(-1) for E-4 and E-5, respectively. It appears that other bioactive compounds, related to E-4 and E-5, are also produced making it the most biologically active endophytic Streptomyces spp. on record.

Animals↗

Pharmacological activities of some Argyranthemum species growing in the Canary Islands.

Methanolic extracts of eight subspecies of genus Argyranthemum were evaluated against brine shrimps, human cancer cell lines, malarial parasites and microorganisms under in vitro conditions. In the shrimp assay, samples of A. adauctum ssp. adauctum, A. adauctum ssp. erythrocarpon and A. frutetescens ssp. succulentum were active with ED50 values in the range of around 300 to 360 microg/ml. In the Caco-2, HepG2 and MCF-7 cell lines, the samples A. adauctum ssp. jacobaeifolium and A. adauctum ssp. palmensis were active with LC50 values ranging between 80-90 microg/ml. The secondary assay results of antimalarial activity of samples, A. adauctum ssp. adauctum, A. adauctum ssp. dugourii, A. adauctum ssp. erythrocarpon and A. adauctum ssp. jacobaeifolium have IC50 values <50 microg/ml. The samples demonstrated broad specific antimicrobial activity against five different microorganisms.

Animals↗

Antimalarial activity from three ascidians: an exploration of different marine invertebrate phyla.

Recent research suggests that marine organisms may produce compounds with activity against malaria parasites. Of a total of 27 aqueous extracts from different marine species, collected on the northwest Cuban coast, 20 were considered as showing no significant activity against Plasmodium falciparum F32, with minimum inhibitory concentrations (MIC) >500 microg/ml, while seven extracts (MIC < or =500 microg/ml) were selected for further investigation by determining their selectivity indices and in vivo antimalarial activity. Three species of tunicates were chosen, as more than 50% reduction of P. berghei parasitaemia was produced after administration of 250 or 500 mg/kg of their crude extracts into infected mice. The aqueous extracts of Microcosmus goanus, Ascidia sydneiensis and Phallusia nigra were partitioned between water and n-butanol; the organic phases inhibited P. falciparum growth by 50% at concentrations of 17.5 microg/ml, 20.9 microg/ml and 29.4 microg/ml respectively. In general, these results are similar to those of most ethnobotanical surveys. Further chemical studies are being undertaken in order to isolate new antimalarial compounds from these Caribbean tunicates.

Animals↗

Monitoring of Plasmodium vivax sensitivity to chloroquine in vitro in Thailand.

The sensitivity of Plasmodium vivax to chloroquine in vitro was investigated in patients admitted to the Bangkok Hospital for Tropical Diseases, Thailand, between September 2001 and May 2002. Of 42 isolates, 34 were successfully tested for parasite sensitivity to chloroquine in vitro; the results showed a significant decrease in sensitivity compared with data published in 1989 and 1995: the IC50 and IC90 were 187.2 and 1217.9 ng/mL blood, respectively, an approximate 4-fold decrease in sensitivity in comparison with other data from the past 2 decades. A number of in vitro tests were performed simultaneously using both WHO microplates and our own laboratory-prepared pre-dosed microplates under the same conditions and there was no significant difference between the results.

Animals↗