Metabolic engineering aimed at monoterpene production has become an intensive research topic in recent years, although most studies have been limited to herbal plants including model plants such as Arabidopsis. The genus Eucalyptus includes commercially important woody plants in terms of essential oil production and the pulp industry. This study attempted to modify the production of monoterpenes, which are major components of Eucalyptus essential oil, by introducing two expression constructs containing Perilla frutescens limonene synthase (PFLS) cDNA, whose gene products were designed to be localized in either the plastid or cytosol, into Eucalyptus camaldulensis. The expression of the plastid-type and cytosol-type PFLS cDNA in transgenic E. camaldulensis was confirmed by real-time polymerase chain reaction (PCR). Gas chromatography with a flame ionization detector analyses of leaf extracts revealed that the plastidic and cytosolic expression of PFLS yielded 2.6- and 4.5-times more limonene than that accumulated in wild-type E. camaldulensis, respectively, while the ectopic expression of PFLS had only a small effect on the emission of limonene from the leaves of E. camaldulensis. Surprisingly, the high level of PFLS in Eucalyptus was accompanied by a synergistic increase in the production of 1,8-cineole and alpha-pinene, two major components of Eucalyptus monoterpenes. This genetic engineering of monoterpenes demonstrated a new potential for molecular breeding in woody plants.

Abstract In this study, antimicrobial activities of the essential oils obtained by using the hydrodistillation method from some lamiaceous plants-Mentha longifolia (L.) Hudson ssp. longifolia, M. longifolia (L.) Hudson ssp. typhoides (Briq.) Harley var. typhoides, Mentha pulegium L., Salvia fruticosa Miller, Salvia tomentosa Miller, Calamintha nepeta (L.) Savi ssp. glandulosa (Req.) P.W. Ball, Nepeta cadmea Boiss., Lavandula stoechas L. ssp. stoechas, and Ziziphora tenuior L.-were determined by using the disc diffusion method. The plants used in this study were collected from different localities of Muğla Province, Turkey. All the essential oils isolated from the plants were very effective against Gram-positive and Gram-negative bacteria, which included multiple-antibiotic resistant strains, except Pseudomonas aeruginosa ATCC 27853 and Pseudomonas fluorescens MU 87. The essential oils of the plant species, except S. tomentosa and S. fruticosa, were very effective against Candida albicans. The antimicrobial activities varied depending on the species, subspecies, or variety. In fact, essential oils of some plants belonging to the same taxa but collected from different localities showed different levels of antimicrobial activities.

The enhancement of the antibacterial activity of ampicillin by different extracts of Berberis integerrima fruits was evaluated against Staphylococcus aureus. Disk diffusion and agar dilution methods were used to determine the antibacterial activity of ampicillin in the absence and presence of different plant extracts or various fractions eluted by column chromatography. A clinical isolate of S. aureus was used as a test strain. The active component of B. integerrima fruits involved in the enhancement of ampicillin activity was purified and identified as 1-methyl malate using different spectroscopic methods. Both the ethanol extract of B. integerrima fruits and 1-methyl malate enhanced the antibacterial activity of ampicillin. The total extract as well as 1-methyl malate increased the antibacterial activity of ampicillin against the test strain. The potency of ampicillin against the test strain was increased 64-fold when tested with a sub-toxic concentration of total extract of B. integerrima fruits. Also, 1-methyl malate increased the bactericidal activity of ampicillin. In the presence of 2 mg/mL of 1-methyl malate the MIC of ampicillin for S. aureus decreased from 128 to 1 microg/mL (128-fold). Copyright (c) 2009 John Wiley & Sons, Ltd.

Salmonellosis is a major bacterial zoonosis that causes a variety of disease syndromes, from self-limiting enteritis to fatal infection in animals and food-borne infection and typhoid fever in humans. Recently, the emergence of multidrug-resistant strains of Salmonella sp. has caused more serious problems in public health. The present study investigated the antibacterial effects of Houttuynia cordata water extract (HCWE) against murine salmonellosis. In RAW 264.7 cells, there was no detectable cytotoxic effect of HCWE at any concentration between 25 and 100 mug/ml after 8-h incubation. The antibacterial activity of HCWE was then examined in a Salmonella enterica serovar (Salmonella typhimurium), and was found to increase in a dose-dependent manner at concentrations from 25 to 100 mug/ml during 8-h incubation. HCWE also affected RAW 264.7 cells including morphologic change and bacterial uptake, but there was no significant difference in bacterial replication in RAW 264.7 cells. With HCWE alone, nitric oxide (NO) production by RAW 264.7 cells did not increase, but when RAW 264.7 cells were infected by S. typhimurium, with or without HCWE, NO production with HCWE was 2-fold higher than that without HCWE. Treatment with HCWE did not affect inducible NO synthase (iNOS) mRNA expression by RAW 264.7 cells, but when RAW 264.7 cells with HCWE were infected by S. typhimurium, iNOS mRNA expression was increased during 8-h incubation. Furthermore, HCWE showed virulence reduction effects in S. typhimurium-infected BALB/c mice. After a lethal dose of S. typhimurium, the mortality rate in the HCWE untreated group was 100% at 7 d, but the HCWE 25, 50, and 100 mug/ml groups survived until 11, 17, and 23 d, respectively. These data suggest that HCWE is stable and beneficial in the treatment of bacterial infection including intracellularly replicating pathogens and may solve antimicrobial misuse and overuse.

This study addresses the adaptive dynamics of plant toxins that ward off herbivores, an aspect of chemical warfare in ecosystems. Thyme basil (Acinos suaveolens) growing in an area regularly grazed by mammals contains double the concentration of monoterpenoids (15.61 vs. 8.18 mg/g dry matter, P = 0.001) when contrasted with plants growing on inaccessible rock pillars and not exposed to mammalian herbivores. Thyme basil produces two monoterpenoids-menthone and R-(+)-pulegone-that show contrasting toxicity. The more toxic R-(+)-pulegone shows an increase in relative abundance (66.3% vs. 47.5%, P < 0.001) in plants exposed to browsing The results demonstrate how plant chemistry responds to both abiotic and biotic environmental conditions.

Therapy with antimicrobial drugs, such as clindamycin, that perturb the intestinal flora but fail to inhibit growth of other microorganisms can permit the proliferation of Clostridium difficile and the elaboration of exotoxin. Therefore, there has been increasing interest in the use of inhibitors of antibiotic resistance for use in combination therapy. The essential oil of Cinnamomum zeylanicum bark enhanced the bactericidal activity of clindamycin and decreased the minimum inhibitory concentration of clindamycin required for a toxicogenic strain of C. difficile. Thin-layer chromatography (TLC) analysis of the essential oil separated a fraction (R(f)= 0.54) that was the most effective at enhancing the clindamycin antimicrobial activity. Using gas liquid chromatography and known standards, the active fraction was identified as trans-cinnamaldehyde (3-phenyl-2-Propenal). Combinations of clindamycin and trans-cinnamaldehyde were tested to determine the fractional inhibitory concentration (FIC) index by conventional checkerboard titration. The FIC index for C. difficile was found to be 0.312, which confirmed the synergistic actions of clindamycin and trans-cinnamaldehyde. The presence of 20 mug/mL of trans-cinnamaldehyde decreased the MIC of clindamycin for C. difficile 16-fold, from 4.0 to 0.25 mug/mL. These results signify that low concentrations of trans-cinnamaldehyde elevate the antimicrobial action of clindamycin, suggesting a possible clinical benefit for utilizing these natural products for combination therapy against C. difficile.

In this study the enhancement effect of Ferula szowitsiana roots' acetone extract on the antibacterial activity of penicillin G and cephalexin was evaluated against Staphylococcus aureus. Disk diffusion and broth dilution methods were used to determine the antibacterial activity of these antibiotics in the absence and presence of plant extract and its various fractions separated by TLC plate. The active component of plant extract involved in enhancement of penicillin G's and cephalexin's activities had Rf=0.336 on a TLC plate. The spectral data ((1)H-,(13)C-NMR) of this compound revealed that this compound was 7-[6-(beta-carboxyethyl)-5-isopropylidene-1,2-dimethylcyclo-hexylmethoxy]coumarin (galbanic acid), previously isolated from Ferula assa-foetida. In the presence of sub-inhibitory concentration of galbanic acid (100 mug/ml) the MIC of penicillin G for S. aureus decreased from 64 to 1 (a sixteen four-fold decrease) and for cephalexin from 128 to 1 mug/ml (a one hundred twenty eight-fold decrease). The highest fold decrease in MIC was observed for cephalexin in combination of galbanic acid against test strain. These results signify that the low concentration of galbanic acid (100 mug/ml) potentiates the antimicrobial action of penicillin G and cephalexin suggesting a possible utilization of these compounds in combination therapy against S. aureus.

The chemical composition of the essential oils obtained by hydrodistillation from the aerial parts of Mentha cervina collected during the flowering and vegetative phases of the plants were investigated by GC and GC-MS. Quantitative differences were observed in the compositions, particularly in the amounts of pulegone (12.9-79.6%) and isomenthone (8.7-77.0%). Antifungal activity of the oils was evaluated by minimal inhibitory concentrations (MIC) and minimal lethal concentrations (MLC) against Candida, Apergillus and dermatophyte strains. Antifungal activity of the sample containing lower amounts of pulegone was the highest for dermatophytes, particularly for Epidermophyton floccosum with MIC and MLC values of 0.63 microL mL(- 1). Mentha cervina oils with low content of pulegone, may be an alternative as antifungal agents in dermatophytosis.

The study reports the effects on volatiles of an endophytic fungus inhabiting asymptomatically the leaves of peppermint. By means of headspace solid-phase microextraction (HS-SPME) and gaschromatography-mass spectrometry (GC-MS) terpenoids were sampled in time course from the head space of peppermint leaves and roots. After removal of the mycelium from peppermint tissues, fungal volatiles were analyzed and compared with those of pure fungal cultures. In the presence of the endophyte, the relative amount of all main compounds increased in leaves. Starting from the first 14 d of culture,(-)-menthone and (+)-neomenthol were consistently higher than in control plants. On the contrary,(+)-menthofuran increased only by 28 d of culture. Root volatiles were also dramatically altered by the presence of the fungus, with (+)-pulegone accounting for at least 44% of the total volatile emission.(+)-Pulegone was also the main compound of PGP-HSF mycelium isolated from peppermint roots. The sesquiterpenoid cuparene was found as a novel compound of peppermint leaf headspace and was a main volatile of ex planta and pure culture mycelia. The chemical spectrum of terpenoids and their distribution among peppermint roots, leaves, and mycelia are likely to account for a fine regulation of the mutualism in planta and for the acquisition by the fungus of novel metabolic competences.

The composition and the antibacterial activity of the essential oil obtained from Cryptomeria japonica D. Don on oral bacteria were studied. The chemical composition of the essential oil was analysed by GC and GC-MS. Sixty-eight compounds accounting for 95.82% of the oil were identified. The main compounds in the oil were alpha-pinene (6.07%), sabinene (8.86%), terpinen-4-ol (9.77%), alpha-terpineol (6.13%), elemol (11.17%) and 10(15)-cadinen-4-ol (7.16%). The essential oil and some of its major compounds were tested for antimicrobial activity against 15 different genera of oral bacteria. The essential oil of C. japonica exhibited considerable inhibitory effects against all bacteria tested (MICs, 0.025-0.05 mg/mL; MBCs, 0.025-0.1 mg/mL), while its major compounds demonstrated various degrees of growth inhibition. Copyright (c) 2007 John Wiley & Sons, Ltd.

Four extracts at increasing polarity were prepared from the leaves of Thymus satureioides Coss.(Labiatae) and assayed for the in vivo topical anti-inflammatory effect using the croton oil ear test in mice, and for in vitro both antioxidant (DPPH degrees test) and anti-bacterial (broth microdilution method) activities. The chloroform extract showed a topical anti-inflammatory activity ([Formula: see text] microgcm(-2)), only three times lower than that of the reference drug indomethacin ([Formula: see text] microgcm(-2)) and its active components were identified as ursolic and oleanolic acids. The methanol extract, showing a significant radical-scavenging effect ([Formula: see text] microg), was characterized by the isolation and identification of some flavonoids. On the contrary, the extracts did not show any anti-bacterial effect against four standard aerobial bacteria strains.

The topical anti-inflammatory activity of four extracts from Thymus broussonetii Boiss (Labiatae) leaves, a herbal drug used in Moroccan traditional medicine, has been studied using the croton oil ear test in mice. A bioassay-oriented fractionation revealed that the pharmacological activity is mainly in the chloroform extract. Fractionation and analysis of this extract allowed the identification of ursolic acid and oleanolic acid as the main anti-inflammatory principles. Some flavonoids (luteolin, eriodictyol, thymonin) and glycosides (luteolin-7-O-glucoside, luteolin-3'-O-glucuronide, eriodictyol-7-O-glucoside) were also isolated from the methanol extract.

The topical anti-inflammatory activity of Thymus willdenowii Boiss (Labiatae) leaves, a herbal drug used in Moroccan folk medicine, has been studied using the croton oil ear test in mice. A bioassay-oriented fractionation procedure showed that the activity concentrates in the chloroform extract, which has a potency similar to that of indometacin, the non-steroidal anti-inflammatory drug used as reference (ID50 (dose giving 50% oedema inhibition)= 83 microg cm(-2) and 93 microg cm(-2), respectively). The main compounds responsible for the anti-inflammatory activity of T. willdenowii are ursolic acid and oleanolic acid. The flavonoids luteolin-3'-O-glucuronide and eriodictyol-7-O-glucoside were found for the first time in the genus Thymus.

A phytochemical study of Moroccan Mentha longifolia was carried out. The essential oil showed unusual relevant amounts of piperitenone oxide and piperitone oxide, which constitute a new chemotype. From the non-volatile extract, five flavonoids were isolated, among which 5,7,4'-trihydroxy-6,2',3'-trimethoxyflavone (1) is reported for the first time.

Leishmaniases in Morocco are endemic diseases. Three forms of leishmaniasis are reported, visceral leishmaniasis, cutaneous leishmaniasis caused by Leishmania tropica and cutaneous lesions due to Leishmania major. Leishmania infantum, a common parasite inducing visceral leishmaniasis, was observed thereafter in cutaneous lesions. The first case of cutaneous leishmaniasis due to L. tropica was isolated since 1987. But, this parasite was shown to be more polymorphic with almost 8 zymodemes. However, these zymodemes are not all transmitted by Phlebotomus sergenti and not all isolated from human reservoir. Regarding the clinical aspect, cutaneous leishmaniasis with L. tropica is described as a single lesion starting as a nodule at the site of inoculation. A crust develops centrally which may fall away exposing an ulcer which heals gradually. The second cutaneous form is that caused by Leishmania major. It was known in villages located in the southern slopes of the Atlas Mountains. Clinically, the lesion is often severely inflamed and ulcerated and heals in 4-6 months. The epidemiologic cycle of this rural form, include Phlebotomus papatasi as the proven vector and a commensally rodent, Meriones shawi grandis as the reservoir. However, visceral leishmaniasis in Morocco has been known since 1921. It is especially located in the North. The responsible parasite is L. infantum MON 1. Two species of the sand fly are involved in the transmission of this form, P. ariasi and P. perniciosus. In infected man, the clinical signs are non-tender splenomegaly, with or without hepatomegaly, wasting and pallor of mucous membranes. Even though L. infantum MON1 is responsible of the disease, some canine cases were reported to be caused by Leishmania tropica.

This study was designed to determine the age-specific rubella seroprevalence in women of childbearing age in Morocco and to contribute to the development of a rubella vaccination strategy in the country. Of 967 women aged 15-39 years tested in 2000, 161 (16.6%) were susceptible to rubella based on absence of IgG antibodies. A significantly higher rate of susceptibility among women aged 15-19 years was observed (29.3%) compared with age 35-39 years (8.3%). An estimated 77,562 live births occur annually to rubella-susceptible women. No statistical difference in seroprevalence was seen between women in rural and urban areas (81.5% and 85.0% respectively). A substantial risk of rubella infection exists for Moroccan women of childbearing age.

SETTING: Two sample panels: 1) 20 pulmonary tuberculosis (PTB) patients and 10 healthy subjects from a country with a low incidence of TB (Italy); and 2) 47 PTB patients and 26 healthy subjects from a country with a high incidence of TB (Morocco). OBJECTIVE: To identify a combination of Mycobacterium tuberculosis peptides useful for the serodiagnosis of active PTB. METHODS: Fifty-seven B-cell epitope peptides of M. tuberculosis were evaluated by immunoenzymatic assay and the data were analysed using logistic regression analysis and the random forest method. RESULTS: The best discriminating peptide between PTB patients and healthy subjects from the sample of the low TB incidence country was the 23 amino acid peptide of the Rv3878 protein. The sensitivity and specificity were respectively 65% and 100%. The same peptide had a sensitivity and specificity of respectively 47% and 100% for the sample from the high TB incidence country. The best combination of peptides was a pool of nine peptides which had a sensitivity of 70.2% and a specificity of 100% in the high TB incidence country. CONCLUSIONS: The 9-peptide pool can be useful in identifying patients with active PTB.

Severe combined immunodeficiency disease (SCID) of horses is an autosomal, recessive hereditary disease occurring among Arabian or crossbred Arabian horses. The genetic defect responsible was previously identified as a 5-base pair deletion in the gene encoding the catalytic subunit of the DNA dependant protein kinase (DNA-PKcs). This study was carried out to determine the frequency of SCID and identify horses carrying the gene for SCID among Arabian and Arabian crossbred stallions and mares in Morocco using a DNA-based test. Twenty-one horses were SCID carriers: 14 (7%) Arabians, 6 (4%) Arab-Barbs and one (33%) Anglo-Arab. After analysing their genealogy, 3 imported stallions were identified that disseminated the mutant gene of DNA-PKcs in Morocco.

To evaluate the risk of malaria transmission resumption in Morocco, we have studied the current level of receptivity of the region of the last malaria focus in the country. Anopheles (Anopheles) maculipennis labranchiae and Anopheles (Cellia) sergentii, the major vectors of malaria in Morocco, are still presents but their anthropothic index was low and no parasite positive samples were detected. An. labranchiae was very rare; only 34 females were caught over all the study period. The human biting rate was nil and none of its blood meal was human. An. sergenti was more abundant but its low human aggressiveness and its zoophilic behaviour would not attribute to this species an important vectorial capacity. Thus, the receptivity of Chefchaouen province, the region of the last malaria focus in Morocco, under the current vector control measures undertaken by Public Health services, is low and despite the likely presence of Plasmodium vivax gametocyte carriers, the malariogenic potential appears to be low and the risk of malaria resumption is, at this time, unimportant.

This article reports on the investigation on the bioactivity of eugenol, limonene, and citrus extract against three bacteria (Lactobacillus plantarum, Lactobacillus brevis, and Bacillus coagulans) and three yeasts (Saccharomyces bayanus, Pichia membranifaciens, and Rhodotorula bacarum), representing the spoilage microflora of fruit juices. The experiments were performed with laboratory media by using a microdilution method. Data were fitted using the Gompertz equation, and the kinetic parameters were used to evaluate the MIC and the dose-dependent effect (at suboptimal doses for each essential oil). Citrus extract was the most effective essential oil, and the results suggested the following susceptibility hierarchy, from the most sensitive microorganism to the most resistant one (values in parentheses represent MICs): S. bayanus (2 ppm)> R. bacarum (3 ppm)> P. membranifaciens (5 ppm)> B. coagulans (cells, 20 ppm)> L. brevis (40 ppm)> L. plantarum (>40 ppm).

The antimicrobial activities of ethanol, methanol and hexane extracts from Artemisia absinthium, Artemisia annua and Artemisia vulgaris were studied. Plant extracts were tested against five Gram-positive bacteria, two Gram-negative bacteria and one fungal strain. The results indicated that Artemisia annua alcoholic extracts are more effective against tested microorganisms. However, all plants extracts have moderate or no activity against Gram-negative bacteria. The obtained results confirm the justification of extracts of Artemisia species use in traditional medicine as treatment for microbial infections.

In the present study we synthesized, characterized and checked the antimicrobial activity of fatty acid analogs of cholesterol. The synthesized compounds were characterized using IR,(1)H NMR,(13)C NMR and mass spectral data and tested for their antimicrobial activity by disk diffusion assay with slight modifications against Gram-positive, Gram-negative strains of bacteria as well as fungal strains. Minimum inhibitory concentration (MIC) of all the synthesized compounds was also determined. Compounds 7-14 showed inhibitory action against both the groups of bacteria and four strains of fungus. In vitro antimicrobial activity of the test compounds show that the compounds 10 and 13 are excellent antibacterial agents, where as compounds 13 and 14 are the excellent antifungal agents among the eight synthesized compounds.

A series of new alpha-hydroxyphosphonate and alpha-acetoxyphosphonate derivatives have been synthesized for the first time of tetrazolo [1, 5-a] quinoline derivatives. Elemental analysis, IR,(1)H NMR,(13)C NMR and mass spectral data elucidated the structures of the all newly synthesized compounds. In vitro antimicrobial activities of the synthesized compounds were investigated against Gram-positive Bacillus subtilis, Gram-negative Escherichia coli and fungi Candida albicans and Aspergillus niger. Some of the tested compounds showed significant antimicrobial activity.

Herein, we report a convenient one-pot synthesis of 2'-amino-5alpha-cholest-6-eno [6,5-d] oxazole derivatives (4-6). The synthesis involves the reaction of cholestan-6-ones (1-3) with urea and iodine. The structural assignment of the products was confirmed on the basis of IR,(1)H NMR,(13)C NMR, and Mass spectra which find support from comparison with authentic samples. The antibacterial activity of all the synthesized compounds was tested in vitro by the disk diffusion assay against three Gram-positive and three Gram-negative strains of bacteria. All the synthesized compounds were also tested for their inhibitory action against five strains of fungus and then the minimum inhibitory concentration (MIC) of all the synthesized compounds were determined. Compounds (4-6) showed inhibitory action against both types of the bacteria (Gram-positive and Gram-negative) and five strains of fungi are good antimicrobial agents. Chloramphenicol (30 microg) was used as standard drug in case of bacteria and nystatin was used as a standard drug in case of fungi.

Using Gossypol (GOS) extracted from cotton seeds, a series of its Schiff bases (1-18) and hydrazones (19-27) have been synthesized and evaluated for their antimicrobial activities against Gram-positive bacteria, Gram-negative bacteria and yeast-like organisms. Of the 27 aza-derivatives of gossypol, 11 have been found active against the microorganisms tested, similar to gossypol. Crystal structures of the new Schiff base (compound 7) and hydrazone (compound 25) of gossypol reveal the presence of two different tautomers within two types of the aza-derivatives studied. The newly synthesized aza-derivatives of gossypol are characterized by the FT-IR, NMR and MS methods.

The volatile components and in vitro antimicrobial activities of Emblica (Phyllanthus emblica L.) essential oils (EOs) obtained by hydrodistillation (HD-EO) and supercritical fluid extraction (SFE-EO) were investigated. The compositions of volatile compounds in these oils were tentatively determined by gas chromatography-mass spectrometry. The antimicrobial activites of these two extracts were investigated with microbiological tests against Gram-positive and Gram-negative bacteria and three pathogenic fungi. The main components of both oils were beta-caryophyllene, beta-bourbonene, 1-octen-3-ol, thymol, and methyleugenol. Both essential oils showed a broad spectrum of antimicrobial activity against all the tested microorganisms. Gram-positive bacteria were more sensitive to the investigated oils than Gram-negative bacteria. SFE-EO exhibited a higher antifungal activity compared to HD-EO.

A series of novel macrocyclic compounds were synthesized by the condensation of o-phthalaldehyde with aromatic amino alcohols followed by treatment with 1,2-dibromoethane or 1,3-dibromopropane in non-template method. The structural features of the isolated macrocycles have been determined from the microanalytical, IR,(1)H,(13)C NMR and mass spectral studies. Antimicrobial activities of these macrocyclic compounds were tested against the Gram-positive (Bacillus subtilis, Staphylococcus aureus) and Gram-negative (Escherichia coli, Klebsiella pneumoniae) bacteria and found to exhibit potential antibacterial activity. The macrocycles were also tested in vitro to evaluate their activity against fungi, namely, Aspergillus flavus (A. flavus) and Fusarium species.

To explore new agents of quinolone derivatives with high activity against Gram-positive and Gram-negative microorganisms, 7-(3-amino-4-alkoxyimino-1-piperidyl) quinolones were designed and synthesized, and their activity against Gram-positive and Gram- negative microorganisms were tested in vivo and in vitro. Twenty one target compounds were obtained. Their structures were established by 1H NMR, HRMS and X-ray crystallographic analysis. The target compounds possess different antimicrobial activities against both Gram-negative and Gram-positive microorganisms. Compounds 14a and 14m have broad spectral antibacterial activities. They show better antibacterial activities against 12 strains Gram-positive bacteria than three references. In particular, their activities against S. aureus and S. epidermidis (including MRSA and MRSE) were 4 - 16 times than that of gemifloxacin and balofloxacin, and 8 - 64 times than that of levofloxacin. The MIC values to S. aureus strains of compounds 14a and 14m were 0.25 - 1 mg x L(-1) and 0.125 - 1 mg x L(-1), to S. epidermidis strains were 0.5 - 4 mg x L(-1) and 1 - 8 mg x L(-1) respectively. The in vivo results showed that they have as good internal protection as gemifloxacin and moxifloxacin against systemic infection model in mice (P > 0.05).

Five new asterric acid derivatives, ethyl asterrate ( 3), n-butyl asterrate ( 4), and geomycins A-C ( 6- 8), have been isolated from cultures of an isolate of the Antarctic ascomycete fungus Geomyces sp. The structures of these metabolites were elucidated by NMR spectroscopy. The absolute configuration of 8 was determined by application of the CD excitation chirality method. Compound 7 displayed antifungal activity against Aspergillus fumigatus, whereas 8 showed antimicrobial activities against Gram-positive and Gram-negative bacteria.