Histidine-rich glycoprotein exerts antibacterial activity

Histidine-rich glycoprotein (HRGP), an abundant heparin-binding protein found in plasma and thrombocytes, exerts antibacterial effects against Gram-positive bacteria (Enterococcus faecalis and Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Fluorescence studies and electron microscopy to assess membrane permeation showed that HRGP induces lysis of E. faecalisbacteria in the presence of Zn2+ or at low pH. Heparin blocked binding of the protein to E. faecalis and abolished antibacterial activity. Furthermore, truncated HRGP, devoid of the heparin-binding and histidine-rich domain, was not antibacterial. It has previously been shown that peptides containing consensus heparin-binding sequences (Cardin and Weintraub motifs) are antibacterial. Thus, the peptide (GHHPH)4, derived from the histidine-rich region of HRGP and containing such a heparin-binding motif, was antibacterial for E. faecalis in the presence of Zn2+ or at low pH. The results show a previously undisclosed antibacterial activity of HRGP and suggest that the histidine-rich and heparin-binding domain of HRGP mediates the antibacterial activity of the protein.     

Non-antibiotic antibacterial activity of dodecyl gallate

Dodecyl (C(12)) gallate (3,4,5-trihydroxybenzoate) (1) was found to possess antibacterial activity specifically against Gram-positive bacteria, in addition to its potent antioxidant activity. The time-kill curve study indicates that this amphipathic gallate exhibits bactericidal activity against methicillin resistant Staphylococcus aureus (MRSA) strains. Dodecyl (lauryl) gallate inhibited oxygen consumption in whole cells and oxidation of NADH in membrane preparation. The antibacterial activity of this gallate comes in part from its ability to inhibit the membrane respiratory chain. As far as alkyl gallates are concerned, their antimicrobial spectra and potency depend in part on the hydrophobic portion of the molecule.     

In vitro antibacterial activity of kasugamycin

Kasugamycin is an aminoglycosidic antibiotic which was initially reported as being of potential use against Pseudomonas. Our evaluation of this antibiotic does not confirm this expectation. The median minimal inhibitory concentration (MIC) of the Pseudomonas strains tested was 250 μg/ml and the bactericidal level was 500 μg/ml. Kasugamycin was found to be slightly more active in a more basic medium (Mycin Assay broth) in which the median MIC for 11 Pseudomonas strains was 125 μg/ml. Kasugamycin manifests a modest degree of serum binding. Kasugamycin did not have any appreciable effect against a variety of bacteria tested. The only exceptions were several species of gram-negative bacteria, against which more satisfactory antibiotics already exist. Further evaluation of kasugamycin for potential human use as an antipseudomonal agent does not appear warranted.     

Synthesis and antibacterial activity of linezolid analogues

Several new compounds of oxazolidinone class were designed and synthesized referring to the structure-activity relationship studies and the synthesis of Linezolid, and their antibacterial activity was studied.     

Synthesis and antibacterial activity of pyrroloaryl-substituted oxazolidinones

A novel series of oxazolidinones containing a pyrroloaryl substituent was synthesized and screened against a representative panel of susceptible and resistant Gram-positive bacteria. Several members of this series were found to have antibacterial activity comparable to or better than linezolid.     

Aryl urea analogs with broad-spectrum antibacterial activity

The preparation and evaluation of novel aryl urea analogs as broad-spectrum antibacterial agents is described. Numerous compounds showed low micromolar minimum inhibitory concentrations (MIC) against both Gram-positive and Gram-negative bacteria. Selected analogs also exhibited in vivo efficacy in a lethal murine model of bacterial septicemia.     

Synthesis and antibacterial activity of egonol derivatives

Synthesis of egonol derivatives, 5-(3'-chloropropyl)-7-methoxy-2-(3',4'-methylenedioxyphenyl)benzofuran 1, 5-(3'-bromopropyl)-7-methoxy-2-(3',4'-methylenedioxyphenyl)benzofuran 2, 3-[2-(1,3-benzodioxol-5-yl)-7-methoxy-1-benzofuran-5-yl]propanal 3, 5-(3'-iodopropyl)-7-methoxy-2-(3',4'-methylenedioxyphenyl)benzofuran 4, 5-[3-(3'-bromopropyloxy) propyl]-7-methoxy-2-(3',4'-methylenedioxyphenyl)benzofuran 5, 3-[2-(1,3-benzodioxol-5-yl)-7-methoxy-1-benzofuran-5-yl]propylmethanoate 6, 3-[2-(1,3-benzodioxol-5-yl)-7-methoxy-1-benzofuran-5-yl]propyloleate 7, 5-[3'-hydroxypropyl]-6-bromo-7-methoxy-2-(3',4'-methylenedioxyphenyl)benzofuran 8, 4-[2-(1,3-benzodioxol-5-yl)-7-methoxy-1-benzofuran-5-yl]butanenitrile 9, 3-[2-(1,3-benzodioxol-5-yl)-7-methoxy-1-benzofuran-5-yl]propylbenzoate 10, 5-[3'-hydroxypropyl]-7-methoxy-3-nitro-2-(3',4'-methylenedioxyphenyl)benzofuran 11 and their antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Candida albicans and Escherichia coli are reported. The starting material egonol 5-[3'-(hydroxy)propyl]-7-methoxy-2-(3', 4'methylenedioxyphenyl)benzofuran was isolated from seeds of Styrax officinalis L. The structural elucidication of these compounds (1-11) was established using 1D ((1)H, (13)C), 2D NMR (HMBC, HMQC, COSY) and LCMS spectroscopic data. While egonol and some synthesised new compounds show similar antibacterial activity and MIC values against S. aureus, B. subtilis, C. albicans and E. coli, other new derivatives show different activity against S. aureus, B. subtilis, C. albicans and E. coli.     

Lipase-catalyzed synthesis and antibacterial activity of N-vanillylnonanamide

N-vanillylnonanamide (VAN) was successfully synthesized from vanillylamine hydrochloride by enzymatic catalysis in supercritical carbon dioxide (SC–CO₂). Five commercial lipases, Novozyme 435, Lipozyme IM, Amano PS, Amano G and Sigma Candida cylindracea type VII, as biocatalysts for VAN synthesis were compared. Lipozyme IM exhibited best yields of tested lipases. Various parameters such as time, temperature, pressure and vanillylamine hydrochloride/nonanoic anhydride ratio that influenced the reaction were investigated. Nonanoic anhydride showed the best acyl donor of the employed substrates. An amidation yield of 40% was obtained when nonanoic anhydride and Lipozyme IM were used at 170 bar and 50 °C for 23 h in SC–CO₂. Besides, addition of 2 mM divalent salts (CuCl₂ and ZnCl₂) significantly increased 11–23% yield of the VAN. The enzyme operational stability suggested that Lipozyme IM maintained over 50 °C of the initial activity for the synthesis of VAN after reuse for 69 h. Furthermore, in vitro, VAN behaved as a potential antibacterial against Escherichia coli.     

Triaminotriazine DNA helicase inhibitors with antibacterial activity

Screening of a chemical library in a DNA helicase assay involving the Pseudomonas aeruginosa DnaB helicase provided a triaminotriazine inhibitor with good antibacterial activity but associated cytotoxicity toward mammalian cells. Synthesis of analogs provided a few inhibitors that retained antibacterial activity and demonstrated a significant reduction in cytotoxicity. The impact of serum and initial investigations toward a mode of action highlight several features of this class of compounds as antibacterials.     

The antibacterial activity of alamethicins and zervamicins

Consistent results were obtained in biological assays of alamethicins on agar gels only when the antibiotics were allowed to diffuse under strictly defined conditions of temperature and time before inoculation. In liquid culture obligatory anaerobic rumen bacteria were sensitive to these antibiotics and in certain cases their ability to produce volatile fatty acids was reduced. Among the bacteria examined there was a 1000-fold difference in their sensitivity. Modifications of the structure of the peptaibol, e.g. substitution of an alanine residue for a 2-methylalanine residue resulted in ca two-fold changes in activity.     

In vitro antibacterial activity of glass-ionomer cements

The in vitro antibacterial activity of the glass-ionomer restorative cements Ketac-Cem, Ketac-Bond, Ketac-Silver and Vitrebond was studied in conjunction with 32 strains of five bacteria involved in the development of caries: Streptococcus spp., Lactobacillus spp., Actinomyces spp., Porphyromonas spp. and Clostridium spp. The agar plate diffusion method was used for the cultures, which included a chlorhexidine positive control. All the glass-ionomer cements tested inhibited bacterial growth, but with considerable differences in the scope of their action. Of the four cements, Vitrebond, a resin-modified glass-ionomer cement, was determined to be the most effective bacterial inhibitor.     

The antibacterial activity of alamethicins and zervamicins

Consistent results were obtained in biological assays of alamethicins on agar gels only when the antibiotics were allowed to diffuse under strictly defined conditions of temperature and time before inoculation. In liquid culture obligatory anaerobic rumen bacteria were sensitive to these antibiotics and in certain cases their ability to produce volatile fatty acids was reduced. Among the bacteria examined there was a 1000-fold difference in their sensitivity. Modifications of the structure of the peptaibol, e.g. substitution of an alanine residue for a 2-methylalanine residue resulted in ca two-fold changes in activity.