Antimicrobial activity and phytochemical screening of serial extracts from leaves of Aegle marmelos (Linn.)

The in vitro antimicrobial activity of serial petroleum ether, chloroform and methanol extracts from leaves of Aegle mawmelos were investigated against bacterial and fungal species. All the extracts exhibited broad spectrum antimicrobial activity with zones of inhibition ranging from 10 to 22 mm against bacteria: Staphylococcus aureus, beta Streptococcus haemolyticus group A, Proteus mimrabilis, Klebsiella pneumoniae, Pseudomonas aenrginosa, Escherichia coli, Salmonella typhi, fungi: Candida albicans, Candida tropicalis and Aspergillusflavus. The minimal inhibitory concentrations (MIC) and the minimal microbicidal concentrations (MMC) of the extracts ranged from 1.25 to 10 mg/mL and 2.5 to 20 mg/mL respectively. Assessment of antibacterial efficacy of different extract revealed that Staphylococcus aureus, beta Streptococcus haemolyticus group A, Pseudomonas aeruginosa and Escherichia coli showed high susceptibility to petroleum ether extract. Proteus mimrabilis, Klebsiella pneumoniae showed high susceptibility to chloroform extract and Salmonella typhi showed high susceptibility to methanol extract. Petroleum ether extract exhibited the highest antifungal efficacy against all tested fungal species. Phytochemical screening revealed the presence of phenols, sterols in petroleum ether and chloroform extracts, whereas tannins, flavonoids, coumarins, saponins and triterpenoids in methanol extract. The ability of the leaf extracts of Aegle manmelos to inhibit growth of bacteria and fungi is an indication of its broad spectrum antimicrobial activity which could be a potential source for development of novel bioactive antimicrobial agents.     

Antimicrobial Activity and Phytochemical Constituents of Leaf Extracts of Cassia auriculata

Plants produce a wide variety of phytochemical constituents, which are secondary metabolites and are used either directly or indirectly in the pharmaceutical industry. ‘For centuries, man has effectively used various components of plants or their extracts for the treatment of many diseases, including bacterial infections. In the present study methanol, chloroform and aqueous extracts of Cassia auriculata leaf were subjected for antimicrobial activity by well-diffusion method against six bacterial strains namely Bacillus cereus, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Proteus mirabilis. The results revealed that the methanol and chloroform extracts exhibited strong inhibitory activity against all the tested organisms (zone of inhibition of 12-20 mm), except Pseudomonas aeruginosa (zone of inhibition 10 mm or nil). The aqueous extracts showed moderate activity by ‘Zone of inhibition ≤12 or nil). The extracts were screened for their phytochemical constituents by standard protocols’ and were shown to contain carbohydrates, proteins, alkaloids, flavonoids, steroids, saponins and tannins. The antibacterial activity of these extracts is possibly linked to the presence of flavonoids, steroid, saponins and/or tannins. Further studies are needed to determine the precise active principles from Cassia auriculata.     

Bio-efficacy of Dioscorea pentaphylla from Midmid-Western Ghats, India

Antibacterial and antifungal activity of crude extracts of medicinally important and traditionally used yam plant, Dioscorea pentaphylla, from mid-Western Ghats was evaluated against 27 bacterial and 5 fungal clinical strains collected of the patients from infectious sources. The clinical strains belonging to their respective species showed concentration-dependent susceptibility toward crude petroleum ether extract, chloroform extract and methanol extract at 100 μg/100 μl. The extracts exhibited predominant antibacterial activity against Staphylococcus aureus (ATCC-20852), Pseudomonas aeruginosa (ATCC-29737) and Klebsiella pneumoniae (MTCC-618), respectively, and five clinically isolated pathogenic fungi, Trichophyton rubrum, Microsporum gypseum, Tricophyton tonsurans, Microsporum audouini, and Candida albicans, with antibacterial drug ciprofloxacin and antifungal drug fluconozole (50 μg/100 μl) as standards. Out of the three extracts, ethanol extracts possessed better minimum inhibitory concentration (MIC) against all the bacterial strains. All the three extracts showed significant activity against all the five fungal pathogen strains. The results are promising and support the traditional use of D. pentaphylla for the treatment of bacterial and fungal infections.     

Antibacterial activities of piperacillin in several fresh clinical isolates

We investigated activity of piperacillin (PIPC) in comparison with 8 antibacterial reference drugs against several fresh clinical strains isolated from patients with infectious diseases in the respiratory tract and after surgical interventions in 1999. The following results were obtained: 1. PIPC had its MIC90 of 0.12-6 micrograms/ml in Gram-positive bacteria (Methicillin susceptible Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus pneumoniae, Enterococcus faecalis) and showed its MIC of 1 microgram/ml or higher in 9 possible PRSP strains out of 38 isolates of S. pneumoniae but there were no possible isolates with evident resistance in other species of bacteria. 2. PIPC showed favorable antibacterial activities as its MIC90 were 2-8 micrograms/ml in Gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, Citrobacter freundii, Pseudomonas aeruginosa, Moraxella (Branhamella) catarrhalis, Haemophilus influenzae), except for P. mirabilis in which its MIC90 was as high as 64 micrograms/ml. 11 out of 39 isolates of P. mirabilis were resistant to other drugs such as PIPC, ABPC, CTM and CZOP. 3. PIPC had its MIC90 of > 128 micrograms/ml in Bacteroides fragilis. From these results, PIPC was considered highly effective in several infections in view of maintaining its favorable antibacterial activities in several causative bacteria even today when 20 years had passed since its first application to clinical practice.     

Yearly changes in antibacterial activities of cefozopran against various clinical isolates between 1996 and 2001--I. Gram-positive bacteria

The in vitro antibacterial activities of cefozopran (CZOP), an agent of cephems, against various clinical isolates obtained between 1996 and 2001 were yearly evaluated and compared with those of other cephems, oxacephems, carbapenems, and penicillins. A total of 1,274 strains in 15 species of Gram-positive bacteria were isolated from the clinical materials annually collected from January to December, and consisted of methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis, Staphylococcus haemolyticus, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus pneumoniae, Enterococcus faecalis, Enterococcus faecium, Enterococcus avium, and Peptostreptococcus spp. CZOP possessed stable antibacterial activities against all strains tested throughout 6 years. The MIC90 of CZOP against MRSA and S. haemolyticus tended to decrease while against S. pneumoniae and Peptostreptococcus spp., tended to increase year by year. However, the MIC90 just changed a little and were consistent with the results from the studies performed until the new drug application approval. Increases in the MIC90 against S. pneumoniae were also observed with ceftazidime (CPR), cefepime (CFPM), flomoxef (FMOX), sulbactam/cefoperazone (SBT/CPZ), and imipenem (IPM). Increases in the MIC90 against Peptostreptococcus spp. were also observed with FMOX, SBT/CPZ, and IPM. In conclusion, the annual antibacterial activities of CZOP against the Gram-positive bacteria did not considerably change. It, therefore, was suggested that CZOP had maintained high antibacterial activity during 6 years of post marketing.     

Changes in the antibacterial activity of chemotherapeutic agents (especially carbapenems) for 10 species of clinical isolates between 1994 and 1996. Surveillance group of the sensitivities of clinical isolates to antibacterial agents

During October and December of each year of from 1994 to 1996, 3,849 strains of 10 species of bacteria were isolated from clinical materials in 21 institutions nationwide. The minimum inhibitory concentrations (MICs) for these bacteria of four carbapenems (imipenem [IPM], panipenem [PAPM], meropenem [MEPM], and biapenem [BIPM]) and other representative antibacterial agents were measured to investigate annual changes in antibacterial activity. Carbapenems showed potent activity against methicillin-sensitive S. aureus (MSSA), S. pneumoniae, E. faecalis, H. influenzae, E. coli, K. pneumoniae, E. cloacae, S. marcescens, and the B. fragilis group, with the activity being stable. However, these drugs showed weak activity against methicillin-resistant S. aureus (MRSA) and P. aeruginosa. The antibacterial activity (MIC90) against the tested organisms generally remained stable. Particularly, there was annual improvement of the MIC90 values of IPM and BIPM for S. pneumoniae, as well as the values of IPM and PAPM for H. influenzae, and those of IPM, PAPM, and BIPM for S. marcescens. On the other hand, the activity of carbapenems (including IPM) against MRSA was not necessarily strong, but there was annual improvement of MIC90 values.     

Antibacterial properties of traditionally used Indian medicinal plants

In search of broad-spectrum antibacterial activity from traditionally used Indian medicinal plants, 66 ethanolic plant extracts were screened against nine different bacteria. Of these, 39 extracts demonstrated activity against six or more test bacteria. Twelve extracts showing broad-spectrum activity were tested against specific multidrug-resistant (MDR) bacteria, methicillin-resistant Staphylococcus aureus (MRSA) and extended spectrum beta-lactamases (ESbetaL)-producing enteric bacteria. In vitro efficacy was expressed in terms of minimum inhibitory concentration (MIC) values of plant extracts. MIC values ranged from 0.32-7.5 mg/ml against MRSA and 0.31-6.25 mg/ml against ESbetaL-producing enteric bacteria. The overall activity against all groups of bacteria was found in order of Plumbago zeylanica > Hemidesmus indicus > Acorus calamus > Camellia sinensis > Terminalia chebula > Terminalia bellerica > Holarrhena antidysenterica > Lawsonia inermis > Mangifera indica > Punica granatum > Cichorium intybus and Delonix regia. In addition, these extracts showed synergistic interaction with tetracycline, chloramphenicol and ciprofloxacin against S. aureus and/or Escherichia coli. The ethanolic extracts of more than 12 plants were found nontoxic to sheep erythrocytes and nonmutagenic, determined by Ames test using Salmonella typhimurium test strains (TA 97a, TA 100, TA 102 and TA 104). Based on above properties, six plants-Plumbago zeylanica, Hemidesmus indicus, Acorus calamus, Punica granatum, Holarrhena antidysenterica and Delonix regia-were further subjected to fractionation-based study. Ethyl acetate, acetone and methanol fractions of more than six plants indicated that the active phytocompounds were distributed mainly into acetone and ethyl acetate fractions, whereas they were least prevalent in methanol fractions as evident from their antibacterial activity against MDR bacteria. Gram-positive and Gram-negative MDR bacteria are almost equally sensitive to these extracts/fractions, indicating their broad-spectrum nature. However, strain- and plant extract-dependent variations in the antibacterial activity were also evident. Time-kill assay with the most promising plant fraction Plumbago zeylanica (ethyl acetate fraction) demonstrated killing of test bacteria at the level lower than its MIC. Further, identification of active constituents in each fraction and their additive and synergistic interactions are needed to exploit them in evaluating efficacy and safety in vivo against MDR bacteria.     

Bioactivity of Roots of Laportea crenulata

The roots of Laportea crenulata Gaud (Urticacae) were collected in Bangladesh and the bioactivity was evaluated by two bioassays. The brine shrimp lethality test and the antibacterial activity were conducted on the different organic solvent root extracts of this plant. In addition minimal inhibitory concentration (MIC) was determined using serial dilution technique. On the brine shrimp lethality bioassay, the petroleum ether, chloroform, and methanol extracts of roots of L. crenulata displayed LC₅₀ values of 20.87, 14.43, and 31.02 μ g/ml respectively. Furthermore, the antibacterial assay on these extracts indicated activity against several pathogenic bacteria. The MIC values against Escherichia coli, Shigella dysenteriae, Salmonella typhi, Bacillus subtilis, and Streptococcus-β -haemolyticus were ranged from 32 to 128 μ g/ml. The positive results on these bioactive extracts should encourage the further investigation of the active principles responsible for these activities.     

Anti-inflammatory and cytotoxic activities of five Veronica species

Biological activities of five Veronica species (Scrophulariaceae), V. cymbalaria, V. hederifolia, V. pectinata var. glandulosa, V. persica and V. polita were studied for their anti-inflammatory and cytotoxic activities. Their methanol extracts showed both the inhibitory activity of nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated macrophages and cytotoxic activity against KB epidermoid carcinoma and B16 melanoma. When the methanol extracts were fractionated between water and chloroform, water fractions significantly inhibited NO production without any cytotoxicity, while chloroform fractions showed cytotoxicity dose-dependently. When the radical scavenging activity was determined using 2,2-diphenyl-1-picryl-hydrazyl (DPPH), water fractions of the five Veronica species scavenged free radicals effectively, suggesting that the inhibitory effect of this species on NO production was due to their radical scavenging activity. On the other hand, chloroform fractions of Veronica species except for V. cymbalaria showed similar cytotoxic activity against KB and B16 melanoma cells.     

Antimicrobial susceptibilityof clinical isolates of aerobic gram-negative bacteria in 2008

We determined MICs of antibacterial agents against 1145 clinical strains of aerobic Gram-negative bacteria (22 species) isolated at 16 Japanese facilities in 2008. MICs were determined using mostly broth microdilution method and antibacterial activity was assessed. Strains producing extended-spectrum beta-lactamases (ESBL) accounted for 3.8% of Escherichia coli, 2.6% of Klebsiella pneumoniae, 6.8% of Klebsiella oxytoca, 5.5% of Proteus mirabilis and 1.8% of Proteus vulgaris. ESBL produced strains were 6.8% at K. oxytoca that increased compared with 3.2% and 5.5% at P. mirabilis that decreased compared with 18.8% in 2006. Among Haemophilus influenzae, 61.7% that decreased compared with 67.7% in 2006, equaled 58.7% in 2004, were strains when classified by penicillin-binding protein 3 mutation. Against Pseudomonas aeruginosa, the activity of most antibacterial agents was similar to that in 2006. Although two antibacterial agents that tobramycin showed an MIC90 of 1 microg/mL and doripenem showed an MIC90 of 4 microg/mL against P. aeruginosa have potent activity. Of all P. aeruginosa strains, 4.3% were resistant to six agents of nine antipseudomonal agents, that decreased compared to 12.2% in 2004 and 5.7% in 2006. Against other glucose-non-fermentative Gram-negative rods, the activity of most antibacterial agents was similar to that in 2006.     

Effect of a novel type of propolis and its chemical fractions on glucosyltransferases and on growth and adherence of mutans streptococci

Flavonoids have been considered the main biologically active components in propolis. However, a new variety of flavonoid-free propolis was recently found and chemically classified as type 6. Because it showed activity against oral microorganisms, this study evaluated the effects of the crude ethanolic extract of this propolis and its chemical fractions on the activity of purified glucosyltransferases (GTFs) and on the growth and adherence of mutans streptococci. The inhibitory effect of propolis extracts on GTF activities was determined either in solution or adsorbed onto saliva-coated hydroxyapatite. Streptococcus mutans Ingbritt 1600, Streptococcus sobrinus 6715, and two clinical isolates of each species were used for antibacterial assays. Susceptibilities to the test extracts were analyzed using the agar diffusion method and by determining the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC); the effect on bacterial adherence to a glass surface was also assessed. The activity of GTFs in solution was effectively inhibited by the ethanolic extract of propolis type 6 (EEP) (>80% inhibition at 0.5 mg/ml), hexane, and chloroform fractions (60-90% inhibition at 100 microg/ml); their inhibitory effects on surface enzymes were less pronounced. The EEP, hexane, and chloroform fractions also showed significant antibacterial activity. The data showed that propolis type 6 remarkably reduced GTF activity and inhibited mutans streptococci growth and adherence; these biological activities are associated with its nonpolar components.     

Post-marketing surveillance of antibacterial activities of cefozopran against various clinical isolates--I. Gram-positive bacteria

As a post-marketing surveillance, the in vitro antibacterial activities of cefozopran (CZOP), an agent of cephems, against various clinical isolates were yearly evaluated and compared with those of other cephems, oxacephems, penicillins, and carbapenems. Changes in the bacterial susceptibility for CZOP were also evaluated with the resistance ratio calculated with breakpoint MIC. Sixteen species (2,363 strains) of Gram-positive bacteria were isolated from the clinical materials annually collected from 1996 to 2001, and consisted of methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), methicillin-susceptible Staphylococcus epidermidis (MSSE), methicillin-resistant Staphylococcus epidermidis (MRSE), Staphylococcus haemolyticus, Staphylococcus saprophyticus, Enterococcus faecalis, Enterococcus faecium, Enterococcus avium, Streptococcus pyogenes, Streptococcus agalactiae, penicillin-susceptible Streptococcus pneumoniae (PSSP), penicillin-intermediate resistant S. pneumoniae (PISP), penicillin-resistant S. pneumoniae (PRSP), Streptococcus milleri group and Peptostreptococcus spp. The antibacterial activity of CZOP either against MSSA or MSSE was preferable (MIC90: 2 or 0.5 micrograms/mL) and comparable to those of other cephems. CZOP was also effective on MRSE (MIC90: 16 micrograms/mL) but not on MRSA. CZOP and other cephems had low antibacterial activity against S. haemolyticus (MIC90: 64 micrograms/mL). The antibacterial activity of CZOP against S. saprophyticus was comparable to or higher than those of other cephems, but the MIC90 of CZOP in 2001 was higher than those in 1996-2000 (32 vs 1-2 micrograms/mL). The antibacterial activity of CZOP against E. faecalis was comparable to that of cefpirome (CPR; MIC90: 16 micrograms/mL) and higher than those of other cephems. No antibacterial activity of CZOP against E. faecium and E. avium was observed, like other drugs. The antibacterial activity of CZOP against S. pyogenes was as potent as those of cefotiam and CPR (MIC90: < or = 0.063 microgram/mL), and, against S. agalactiae, was also preferable (MIC90: 0.125 microgram/mL). CZOP indicated preferable antibacterial activity either against PSSP, PISP, or PRSP (MIC90: 0.25, 1, or 2 micrograms/mL). The antibacterial activity of CZOP against S. milleri group was also preferable, but the MIC90 of CZOP in 2001 was higher than those in 1996-2000 (4 vs 0.5 micrograms/mL). The antibacterial activity of CZOP against Peptostreptococcus spp. was preferable but weaker than those of cefazolin and cefmetazole. The resistance ratio estimated from breakpoint MIC of CZOP was 95.9% in MRSA, 93.5% in PRSP, 63.3% in PISP, 35.8% in S. haemolyticus, 27.9% in E. faecalis, and 13.3% MRSE. Those resistance ratios were comparable to those for cefepime (CFPM), but E. faecalis showed 91.2% for CFPM. The difference in the resistance ratio of E. faecalis demonstrated that CZOP successfully maintained its antibacterial activity against these species. In correlation of drug susceptibility, 40.3% of PRSP was not inhibited at breakpoint MIC either CZOP or CFPM while 69.2% at breakpoint MIC either CZOP or ceftazidime. In conclusion, the antibacterial activities of CZOP against the Gram-positive bacteria obtained from the 6-year duration study were consistent with the results from the studies performed until the new drug application approval. A decline in the sensitivities of S. saprophyticus, S. milleri group, PISP, and PRSP to CZOP, however, was suggested.     

海洋链霉菌Streptomyces sp. S598中抗菌活性产物的研究

目的 对海洋链霉菌Streptomyces sp. S598固体发酵提取物的抗菌成分进行研究。方法 采用葡聚糖凝胶Sephadex LH-20、反相柱色谱、硅胶柱层析及半制备HPLC等方法分离纯化该菌株的活性次级代谢产物,并通过ESI-MS、NMR等波谱技术结合文献对比鉴定其结构。结果 从10L固体发酵提取物中分离得到5个单体化合物,分别鉴定为缬氨霉素(1)、二活菌素(2)、亚油酸(3)、亚油酸甲酯(4)和油酸(5)。结论 海洋链霉菌Streptomyces sp. S598能代谢产生具有多种生物活性的化合物。化合物1对MRSA 28300和白念珠菌(ATCC10231)的MIC为1μg/mL,化合物2具有较强的广谱抗细菌活性,对肺炎链球菌、流感嗜血菌的MIC为0.125μg/mL,尤其具有显著的抗MRSA的活性,对MRSA 28300的MIC<0.125μg/mL。化合物1和2均为首次从该种放线菌中分离得到,且本文首次报道其对MRSA均具有抑制活性。     

Antibacterial activity and in vitro cytotoxicity of extracts and fractions of Parkia biglobosa (Jacq.) Benth. stem bark and Ageratum conyzoides Linn. leaves

Many species of plants in African countries are widely used in the rural communities where there is little or no access to modern medicine. However, the safety and effectiveness of these medicinal plants are poorly evaluated. The stem bark of Parkia biglobosa Jacq. and leaves of Ageratum conyzoides Linn. were investigated for their antibacterial and cytotoxic activities. The plant materials were extracted with 95% ethanol, and fractionated with petroleum ether, chloroform and ethyl acetate. The antibacterial effects of the extracts and fractions of the plant materials were assayed on the bacterial cultures of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Methicillin Resistant Staphylococcus aureus (MRSA) and Clostridium perfringes. Ethanol extracts of P. biglobosa and A. conyzoides were screened for cytotoxicity using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay. Two cancer cell lines (SK-MES 1 and SK-LU 1) and one normal cell line (human skin fibroblast cell line, FS5) were used for the screening of the extracts and the fractions obtained. The ethanolic extracts and fractions of P. biglobosa and A. conyzoides showed the best activity against E. coli, S. aureus and MRSA. All fractions of A. conyzoides leaves have no activity against P. aeruginosa. Human lung cancer cell lines (SK-LU 1 and SK-MES 1) and human skin fibroblast cell line (FS5 cells) were treated with various concentrations (3.9μg/ml-2mg/ml) of the extracts and fractions for 24h. SK-MES 1 cells are more susceptible to treatment with the plant fractions. All the fractions of A. conyzoides leaves and the petroleum ether fraction of P. biglobosa were cytotoxic to SK-MES 1 cells, which to some extent may support their traditional inclusion in herbal preparations for treatment of cancer. The overall results provided evidence that the studied plant extracts might be potential sources of new antibacterial and anticancer drug.     

Evaluation of Antibacterial Activities of Medicinal Plants Widely Used Among AIDS Patients in Thailand

Abstract

Antibacterial activity of 12 selected Thai medicinal plants used as self-medication by HIV/AIDS patients in Thailand was studied. Thirty-nine chloroform, methanol, and aqueous extracts from these plants were investigated for their antibacterial activity against important pathogenic bacteria commonly associated with AIDS infection. These included Staphylococcus aureus., methicillin-resistant Staphylococcus aureus. (MRSA), Streptococcus mutans., and Salmonella typhi.. Inhibition of growth was tested using paper disk agar diffusion method. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined by agar microdilution method and agar dilution method in Petri dishes with millipore filters. The Gram-positive bacteria were proved to be susceptible to the chloroform extracts of Alpinia galanga. (L.) Willd., Boesenbergia rotunda. Mansf. (L.), Piper betle. (L.), Spilanthes acmella. (L.) Murray, and Zingiber zerumbet. (L.) Roscoe ex Sm. and the methanol extract of Boesenbergia rotunda.. Chloroform extract of Alpinia galanga. demonstrated the greatest inhibition zones of 29.1 and 23.7 mm against Staphylococcus aureus. and MRSA, respectively. The MIC values of this extract against Staphylococcus aureus. and MRSA were 128 and 256 µg/ml and the MBC values were 256 and 256 µg/ml, respectively. An active compound, 1′-acetoxy-chavicol acetate, was identified with MIC values against MRSA and Staphylococcus aureus. of 64 and 128 µg/ml, respectively.     

Synthesis of Mannich bases of some 2,5-disubstituted 4-thiazolidinones and evaluation of their antimicrobial activities

5-Phenyl/methyl-5-morpholinomethyl/pyrrolidinomethyl-2-(5- aryl-1,3,4-oxadiazol-2-yl)imino]-4-thiazolidinones (5a-m) were synthesized by the reaction of 5-phenyl/methyl-2-[(5-aryl-1,3,4-oxadiazol -2-yl)imino]-4-thiazolidinones (4a-j) with formaldehyde and morpholine or pyrrolidine. The structures of the compounds were determined by analytical and spectral (IR, 1H-NMR, EIMS) methods. The antibacterial activities of the novel compounds against Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, Escherichia coli ATCC 8739, Klebsiella pneumoniae ATCC 4352, Pseudomonas aeruginosa ATCC 1539, Salmonella typhi, Shigella flexneri and Proteus mirabilis and antifungal activity against Candida albicans ATCC 10231 were tested using the disk diffusion method. Compounds 5a, 5b, 5c, 5e, 5g, and 5h were found to be active against S. aureus ATCC 6538 (MIC: 312.5; 39; 19.5; 39; 156; and 78 micrograms/mL respectively) and compounds 5c and 5h against S. flexneri (MIC: both 312.5 micrograms/mL). The minimal inhibitory concentrations of these compounds were determined using the micro dilution method.     

In vitro activities of levofloxacin and other antibiotics against fresh clinical isolates

In this study, the in vitro activity of levofloxacin (LVFX) against 1,020 fresh bacterial clinical isolates was compared with the activities of a range of ofloxacin, ciprofloxacin (CPFX), ampicillin (ABPC), cefaclor, cefpodoxime, methicillin and benzylpenicillin. The clinical isolates except Vibrio cholerae were collected in Japan during 1998 from patients with infectious diseases. MICs were determined using the agar dilution method according to the recommendations by the Japan Society of Chemotherapy. Some isolates of methicillin resistant Staphylococcus aureus (MRSA) and coagulase negative Staphylococcus were resistant to fluoroquinolones, but the MIC50 of LVFX against MRSA was 6.25 micrograms/ml. LVFX was the most active against MRSA among the antibiotics tested. Most of Staphylococcus epidermidis strains were susceptible to the fluoroquinolones. LVFX showed greater activity against all streptococci strains compared with fluoroquinolones tested. In particular, all Streptococcus pneumoniae strains including PRSP were susceptible to LVFX at < or = 1.56 micrograms/ml. Among Enterococcus, ABPC showed superior activity against Enterococcus faecalis but many isolates of Enterococcus species were resistant to ABPC. LVFX was more active against to these Enterococcus species compared with other fluoroquinolones. On the other hand, LVFX and CPFX showed similar activity against isolates of Enterobacteriaceae. CPFX had an MIC50/90 of 0.20, 0.39 microgram/ml and LVFX showed an MIC50/90 of 0.78, 1.56 micrograms/ml against Pseudomonas aeruginosa. LVFX (MIC50/90 0.10, 0.20 microgram/ml) was more active against Acinetobacter species than CPFX (MIC50/90 0.10, 0.39 microgram/ml). Haemophilus influenzae, Branhamella (Moraxella) catarrhalis and V. cholerae were inhibited by low concentration of the fluoroquinolones tested. The MIC90 of LVFX and CPFX were < or = 0.10 microgram/ml against above three species. Some isolates of Neisseria gonorrhoeae and Campylobacter species were moderately resistant to the fluoroquinolones tested but the MIC50 of LVFX and CPFX were < or = 0.39 microgram/ml. Among anaerobes, Propionibacterium acnes was more susceptible than Peptostreptococcus species, and the MIC90 of beta-lactams and fluoroquinolones tested were < or = 0.78 microgram/ml. In conclusion, this study, performed on large number of strains, confirmed an excellent and wide spectrum antibacterial activity of LVFX compared with the fluoroquinolones and beta-lactams tested. And our results suggest that LVFX may be useful in the treatment of various bacterial infections.     

7-[3-氨甲基-4-(脲亚氨基)吡咯烷-1-基]喹诺酮衍生物的合成与抗菌作用研究

目的 寻找新的喹诺酮类抗菌药.方法 设计合成7-位具有较强亲水性取代基的7个氟喹诺酮衍生物,测定其体外抗菌活性.结果 化合物10对金葡菌(包括MRSA)和表葡菌(包括MRSE)的活性(MIC:0.06～4μg/mL)与左氧氟沙星和吉米沙星基本相当.化合物11对肺炎链球菌08-2的活性(MIC:0.25μg/mL)分别是左氧氟沙星和吉米沙星的128倍和32倍,化合物12对肺炎克雷伯菌09-22和09-23的活性(MIC:1μg/mL)分别是左氧氟沙星和吉米沙星的16倍和4倍,但目标物对革兰阴性菌的活性普遍弱于对照药.结论 7-位取代基的水溶性并非决定喹诺酮抗菌活性的主要因素.     

海洋链霉菌Streptomyces sp. S598中抗菌活性产物的研究

目的 对海洋链霉菌Streptomyces sp. S598固体发酵提取物的抗菌成分进行研究。方法 采用葡聚糖凝胶Sephadex LH-20、反相柱色谱、硅胶柱层析及半制备HPLC等方法分离纯化该菌株的活性次级代谢产物,并通过ESI-MS、NMR等波谱技术结合文献对比鉴定其结构。结果 从10L固体发酵提取物中分离得到5个单体化合物,分别鉴定为缬氨霉素(1)、二活菌素(2)、亚油酸(3)、亚油酸甲酯(4)和油酸(5)。结论 海洋链霉菌Streptomyces sp. S598能代谢产生具有多种生物活性的化合物。化合物1对MRSA 28300和白念珠菌(ATCC10231)的MIC为1μg/mL,化合物2具有较强的广谱抗细菌活性,对肺炎链球菌、流感嗜血菌的MIC为0.125μg/mL,尤其具有显著的抗MRSA的活性,对MRSA     

Anti-methicillin resistant Staphylococcus aureus (MRSA) compounds isolated from Laurus nobilis

We found that an extract from Laurus nobilis L. (Lauraceae) leaves showed antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). We purified two flavonoids as the effective compounds and identified them as kaempferol 3-O-alpha-L-(2',4'-di-E-p-coumaroyl)-rhamnoside (C2) and kaempferol 3-O-alpha-L-(2'-Z-p-coumaroyl-4'-E-p-coumaroyl)-rhamnoside (C3). Both compounds showed strong antibacterial activity not only against MRSA but also against vancomycin-resistant enterococci (VRE). There was low or no antibacterial activity of C2 and C3 for Streptococcus pneumoniae, Pseudomonas aeruginosa and Serratia marcescens.