Solid-phase synthesis and antibacterial activity of hydroxycinnamic acid amides and analogues against methicillin-resistant Staphylococcus aureus and vancomycin-resistant S. aureus

A library of hydroxycinnamic acid amides (HCAAs) and analogues were synthesized using solid-phase synthesis technique. These compounds were screened for antibacterial against methicillin-resistant Staphylococcus aureus (MRSA) (11 strains) and vancomycin-resistant S. aureus (VRSA) (4 strains). Dihydrocaffeoyl analogues showed activity against VRSA which were better than the reference drugs, vancomycin and oxacillin. These compounds also exhibited antibacterial activity against MRSA, which were more potent than oxacillin.     

Synthesis and potent antimicrobial activity of some novel 2-phenyl or methyl-4H-1-benzopyran-4-ones carrying amidinobenzimidazoles

Series of flavones and methyl-4H-1-benzopyran-4-ones carrying mono or diamidinobenzimidazoles at different positions were synthesized and evaluated for antibacterial and antifungal activities against E. coli, S. aureus, MRSA (methicillin-resistant S. aureus), MRSE (methicillin-resistant S. epidermidis), S. faecalis and C. albicans, C. krusei. The results showed that while all diamidines are inactive, the compounds having monoamidinobenzimidazoles at the C-6 position of the 2-phenyl-4H-1-benzopyran-4-one have potent antibacterial activities, particularly, against Gram-positive bacteria. Compounds 23 and 22 exhibited the best inhibitory activity with MIC values of 1.56 microg/ml against S. aureus, MRSA, MRSE and 3.12 microg/ml against C. albicans, respectively.     

Synthesis and antimicrobial activity of some new thiazolyl thiazolidine-2,4-dione derivatives

In this study, a series of thiazolyl thiazolidine-2,4-dione derivatives (Va-f and VIa-f) were synthesized and evaluated for their antibacterial and antifungal activities against Staphylococcus aureus (ATCC 25923), methicillin resistant S. aureus (MRSA ATCC 43300), methicillin resistant S. aureus (MRSA isolate), and Escherichia coli (ATCC 23556) and C. albicans (ATCC10145). All the compounds were found active against used microorganisms.     

Antibacterial and bactericidal activities of tea extracts and catechins against methicillin resistant Staphylococcus aureus]

We examined tea extract, (-) epigallocatechin gallate (EGCg) and theaflavin digallate (TF3) for their antibacterial and bactericidal activities against methicillin resistant Staphylococcus aureus (MRSA) and food poisoning strains of S. aureus. Twenty percent tea extract (50 microliters), EGCg (63 micrograms) and TF3 (125 micrograms) added to one ml of culture medium each inhibited the growth of all strains of MRSA and food poisoning S. aureus tested. Tea extract showed also a bactericidal activity against MRSA even at the same concentration of as in ordinarily brewed tea. EGCg at a concentration of 250 micrograms/ml showed a bactericidal activity against MRSA but not against food poisoning S. aureus, but at 500 micrograms/ml reduced markedly the viable number within 48h. These results suggest that tea and catechin can be used as prophylactic agents against MRSA infection.     

Synthesis and potent antimicrobial activity of some novel methyl or ethyl 1H-benzimidazole-5-carboxylates derivatives carrying amide or amidine groups

A series of benzimidazole-5-carboxylic acid alkyl ester derivatives carrying amide or amidine substituted methyl or phenyl groups at the position C-2 were synthesised and evaluated for antibacterial and antifungal activities against S. aureus, methicillin resistant S. aureus (MRSA), S. faecalis, methicillin resistant S. epidermidis (MRSE), E. coli and C. albicans. The results showed that while all simple acetamides are essentially inactive, aromatic amides and amidines have potent antibacterial activities. Aromatic amidine derivatives 13 f-h exhibited the best inhibitory activity with 1.56-0.39 microg/mL MIC values against MRSA and MRSE.     

Detection and partial characterisation of two antibacterial factors from the excretions/secretions of the medicinal maggot Lucilia sericata and their activity against methicillin-resistant Staphylococcus aureus (MRSA)

Maggot therapy is a simple and highly successful method for cleansing infected and necrotic wounds. The use of maggots has become increasingly important in the treatment of non-healing wounds, particularly those infected with the multidrug-resistant pathogen, methicillin-resistant Staphylococcus aureus (MRSA). The increasing challenge concerning the treatment of MRSA infections and the recent finding of vancomycin-resistant strains of MRSA have elicited the search for novel antibacterial compounds and, in particular, investigations into the potent antibacterial mechanism(s) behind maggot therapy. In this study, we report that excretions/secretions (ES) from the blowfly, Lucilia sericata, exhibit potent, thermally stable, protease resistant antibacterial activity against MRSA in vitro. We describe the initial characterisation of two antibacterial factors from native ES of L. sericata. A small, <500 Da factor with significant antibacterial activity against MRSA was partially isolated using ultrafiltration techniques. The potent activity of this factor was comparable to that of native excretions/secretions. A larger, 0.5-3-kDa factor with significant activity against S. aureus was also partially characterised.     

Synthesis and anti Methicillin resistant Staphylococcus aureus activity of substituted chalcones alone and in combination with non-beta-lactam antibiotics

A total of 30 chalcone analogues was synthesized via a base catalyzed Claisen Schmidt condensation and screened for their in vitro antibacterial activity against Methicillin-sensitive Staphylococcus aureus (MSSA) and Methicillin-resistant Staphylococcus aureus (MRSA) alone or in combination with non beta-lactam antibiotics namely ciprofloxacin, chloramphenicol, erythromycin, vancomycin, doxycycline and gentamicin. In the checkerboard technique, fractional inhibitory concentration indices (FICI) show that the following combinations like ciprofloxacin with 25 (4'-bromo-2-hydroxychalcone); doxycycline with 21 (4-hydroxychalcone); doxycycline with 25; and doxycycline with 4 (2',2-dihydroxychalcone) were synergistic against MRSA. In term SAR study, the relationship between chalcone structure and their antibacterial activity against S. aureus and synergy with tested antibiotics were discussed. Possible mechanisms for antibacterial activity of chalcones alone as well as the synergistic effect in combinations were proposed by molecular modeling studies, respectively. Combinations of chalcones with conventional antibiotics could be an effective alternative in the treatment of infection caused by MRSA.     

Development of a bioactive fiber with immobilized synthetic peptides designed from the active site of a beetle defensin

The 9-mer peptides RLYLRIGRR and RLLLRIGRR were immobilized to amino-functionalized cotton fibers by a modification of the SPOT synthesis technique. The antibacterial activities of the peptide-immobilized cotton fibers against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) were investigated. Antibacterial assays revealed that these fibers inhibit the growth of MRSA and the antibacterial activities were maintained after washing and sterilization by autoclaving. The anticancer effect of the peptide-immobilized fiber was also investigated with mouse myeloma cells and human leukemia cells. These results indicate that these fibers have strong growth inhibition activity against bacteria and cancer cells.     

Antimicrobial activity of hydrophobic xanthones from Cudrania cochinchinensis against Bacillus subtilis and methicillin-resistant Staphylococcus aureus

Ten xanthones with one or two isoprenoid groups and a prenylated benzophenone isolated from roots of Cudrania cochinchinensis (Moraceae) were tested for their antimicrobial activities against Bacillus subtilis and methicillin-resistant Staphylococcus aureus (MRSA). Among these compounds, gerontoxanthone H exhibited considerable antibacterial activity against B. subtilis (MIC = 1.56 microg/ml). Four xanthones, gerontoxanthone I, toxyloxanthone C, cudraxanthone S, and 1,3,7-trihydroxy-2-prenylxanthone, showed weak antibacterial activity against the bacterium (MICs = 3.13-6.25 microg/ml). These compounds also exhibited similar MIC values against methicillin-sensitive S. aureus, MRSAs, and Micrococcus luteus.     

Effect of varying the 4'-position of arbekacin derivatives on antibacterial activity against MRSA and Pseudomonas aeruginosa

4'-Deoxy-4'-episubstituted arbekacin derivatives and 4'-epi-5-deoxy-5-episubstituted arbekacin derivatives were designed and synthesized. Arbekacin and 4'-epiarbekacin both displayed the same antibacterial activity against Staphylococcus aureus (including methicillin-resistant S. aureus (MRSA)) and Pseudomonas aeruginosa. The 4'-epi-5-deoxy-5-episubstituted arbekacin derivatives showed potent antibacterial activity. Among them, the antibacterial activity of 5,4'-diepiarbekacin was superior to that of arbekacin or 5-episubstituted arbekacin against Gram-positive and Gram-negative bacteria. The 6'-N-methyl derivative of the 5,4'-diepiarbekacin was effective against P. aeruginosa expressing an aminoglycoside-modifying enzyme AAC(6')-Ib.     

The antibacterial activity against MRSA strains and other bacteria of a <500Da fraction from maggot excretions/secretions of Lucilia sericata (Diptera: Calliphoridae)

The application of Lucilia sericata larvae to chronic, infected wounds results in the rapid elimination of infecting microorganisms, including MRSA. Previously, we demonstrated in vitro antibacterial activity of native excretions/secretions (nES) from L. sericata and partially purified two low mass antibacterial compounds with masses of 0.5-10kDa and <500Da. The present study reports the antibacterial effects of the <500Da fraction (ES<500) on the growth and morphology of a range of bacteria, including 12 MRSA strains. Distinct morphological changes were observed in Bacillus cereus and Escherichia coli following exposure to ES<500. Flow cytometry and confocal microscopy analyses, in conjunction with turbidometric and CFU assays, revealed bacteriostatic activity of nES against S. aureus and E. coli. ES<500 also demonstrated bacteriostatic activity against S. aureus, however, bactericidal activity and the induction of a viable but non-culturable state were observed with ES<500-treated E. coli.     

Antibacterial action of ether oils of some plants

Inhibitory effect of clove oil on Escherichia coli, Staphylococcus aureus, Salmonella typhimurium, Shigella dysenteriae and Candida albicans was detected. Mint ether oil had the high antibacterial action on S. aureus, however against other microorganisms mint oil had a reliably low effect then clove oil. Fennel oil had high antibacterial effect on C. albicans, and bactericidal action on S. typhimurium and S. dysenteriae.     

Synthesis and antibacterial activity of 5-deoxy-5-episubstituted arbekacin derivatives

5-Deoxy-5-episubstituted arbekacin derivatives have been designed and efficiently synthesized. The synthetic compounds showed potent antibacterial activity against both Staphylococcus aureus, including methicillin-resistant S. aureus, and Pseudomonas aeruginosa. In particular, these derivatives were superior to arbekacin against MRSA strains expressing the bifunctional aminoglycoside-modifying enzyme AAC(6')-APH(2'). The antibacterial activity of the 5-deoxy-5-episubstituted arbekacin derivatives against Pseudomonas aeruginosa was markedly influenced by the efflux system of MexXY/OprM. The 6'-N-methyl derivative of the 5-epi arbekacin was effective against Pseudomonas aeruginosa expressing the aminoglycoside-modifying enzyme AAC(6').     

Antibacterial properties of antimicrobial-finished textile products

The antibacterial properties of five kinds of antimicrobial-finished textile products (AFTPs) were examined against Staphylococcus aureus, including methicillin-resistant (MRSA) strains and Pseudomonas aeruginosa, under wet and dry conditions. Textile products containing Ag. Zn. ammonium Zeolite and chitosan were found to be effective against methicillin-sensitive S. aureus (MSSA) for up to 6 hr of incubation under wet and dry conditions, and effective against MRSA for up to 24 hr of incubation only under wet conditions. Under dry conditions, however, all AFTPs were ineffective against one MRSA strain. When organic matter was added to the incubation mixture, textile products containing Ag. Zn. ammonium Zeolite and chitosan still showed antibacterial activities, but not as strongly. The results of this study suggested the following: (1) There are differences in antibacterial properties among commercially available AFTPs; (2) Determining effectiveness requires several hours of incubation; (3) Water content as an environmental factor can affect effectiveness; and (4) Some bacterial species and strains are not affected by AFTPs. The antibacterial properties of AFTPs in the clinical setting may be of limited value.     

The antibacterial activity of plaunotol against Staphylococcus aureus isolated from the skin of patients with atopic dermatitis.

Plaunotol was tested for possible antibacterial activity against twenty strains of methicillin-resistant Staphylococcus aureus (MRSA) and fourteen strains of methicillin-sensitive S. aureus (MSSA) which had been isolated from the skin of patients with atopic dermatitis under growth-promoting conditions. Plaunotol was effective against all strains tested. The dose of plaunotol for 50% inhibition of growth (ID50) ranged from 2.5 to 16 micrograms/ml for strains of MRSA and from 2.5 to 7.0 micrograms/ml for those of MSSA. These results suggest that plaunotol may be useful in the prevention of infection by MRSA and in skin care for patients with atopic dermatitis.     

铜绿假单胞菌抗菌物质对耐甲氧西林金黄色葡萄球菌的抑菌活性研究

目的观察铜绿假单胞菌抗菌物质对耐甲氧西林金黄色葡萄球菌(methicillin-resistant Staphylococcusaureus,MRSA)的体外抑菌活性。方法用交叉划线接种方法进行铜绿假单胞菌对32株耐甲氧西林金葡菌的体外抗菌活性的测定。结果铜绿假单胞菌抗菌物质对MRSA的体外抑菌活性良好,产生色素的菌株的抗菌活性最好,15株铜绿假单胞菌中,7株产蓝绿色色素的铜绿假单胞菌,对MRSA的抑制率均达到了100%,平均抑菌带的宽度为37.7 mm。结论铜绿假单胞菌抗菌物质对32株MRSA具有较强的抗菌活性,无疑对MRSA感染的抗菌药物研制方面开辟了一条新的途径。这是国内的首次研究报道。     

白木香内生真菌Aspergillus sp.A14的挥发性成分及其抗菌活性

通过溶剂萃取法提取白木香内生真菌A14(Aspergillus sp.)的挥发油,采用滤纸片琼脂扩散法分别测定了其对3种人体病原菌的体外抑菌活性。结果表明:A14挥发油对金黄色葡萄球菌(Staphylococcus aureus)、耐甲氧西林金黄色葡萄球菌(Methicillin-resistant S.aureus,MRSA)和白色念珠菌(Candida albicans)均表现出一定抑制作用。应用GC-MS技术,分析鉴定了内生真菌A14挥发油的14个化学成分,显示蜂蜜曲菌素是其中的主要成分,占挥发油峰面积的93.41%。     

Antibacterial activity and mechanism of a scorpion venom peptide derivative in vitro and in vivo

BmKn2 is an antimicrobial peptide (AMP) characterized from the venom of scorpion Mesobuthus martensii Karsch by our group. In this study, Kn2-7 was derived from BmKn2 to improve the antibacterial activity and decrease hemolytic activity. Kn2-7 showed increased inhibitory activity against both gram-positive bacteria and gram-negative bacteria. Moreover, Kn2-7 exhibited higher antibacterial activity against clinical antibiotic-resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA). In addition, the topical use of Kn2-7 effectively protected the skin of mice from infection in an S. aureus mouse skin infection model. Kn2-7 exerted its antibacterial activity via a bactericidal mechanism. Kn2-7 killed S. aureus and E. coli rapidly by binding to the lipoteichoic acid (LTA) in the S. aureus cell wall and the lipopolysaccharides (LPS) in the E. coli cell wall, respectively. Finally, the hemolytic activity of Kn2-7 was significantly decreased, compared to the wild-type peptide BmKn2. Taken together, the Kn2-7 peptide can be developed as a topical therapeutic agent for treating bacterial infections.     

Verrulactones A and B, new inhibitors of Staphylococcus aureus enoyl-ACP reductase produced by Penicillium verruculosum F375

New dimeric compounds of alternariol class, verrulactones A and B, were isolated from a culture broth of the fungal strain Penicillium verruculosum F375 and their structure were established by various spectral analysis. Verrulactones A and B strongly inhibited Staphylococcus aureus enoyl-ACP reductase with IC(50) of 0.92 and 1.41 μM, respectively, and also showed antibacterial activity against S. aureus and MRSA with MICs of 8 and 16 μg/mL, respectively.     

Comparison of the effects in vitro of tea tree oil and plaunotol on methicillin-susceptible and methicillin-resistant strains of Staphylococcus aureus

The effects in vitro of tea tree oil (TTO) and plaunotol were examined by monitoring the growth of a standard strain of Staphylococcus aureus FDA 209P and of fourteen methicillin-susceptible strains of S. aureus (MSSA), together with twenty methicillin-resistant strains (MRSA). The minimum inhibitory concentrations (MIC) and the doses for 50% inhibition of growth (ID50) were determined by the micro-broth dilution (MD) method, and the broth dilution with shaking (BDS) method, respectively. The MIC of plaunotol for 50 and 90% of the MSSA and MRSA were assessed by the MD method, as 16 microg/ml and > or = 1,024 microg/ml, respectively. No antibacterial effects of TTO on MSSA and MRSA were detected by the MD method. The growth-inhibitory effects of TTO on S. aureus by the BDS method were examined, and it appeared that TTO was effective over a lower range of concentrations than previously reported. It seems that TTO is very effective in vitro against MSSA and MRSA at high concentrations but less effective below 40 microg/ml of TTO.