Evaluation of antiseptic antiviral activity of chemical agents.

Antiviral antisepsis and disinfection are crucial for preventing the environmental spread of viral infections. Emerging viruses and associated diseases, as well as nosocomial viral infections, have become a real issue in medical fields, and there are very few efficient and specific treatments available to fight most of these infections. Another issue is the potential environmental resistance and spread of viral particles.

Antiseptic properties of two calix[4]arenes derivatives on the human coronavirus 229E.

Facing the lack in specific antiviral treatment, it is necessary to develop new means of prevention. In the case of the Coronaviridae this family is now recognized as including potent human pathogens causing upper and lower respiratory tract infections as well as nosocomial ones. Within the purpose of developing new antiseptics molecules, the antiseptic virucidal activity of two calix[4]arene derivatives, the tetra-para-sulfonato-calix[4]arene (C[4]S) and the 1,3-bis(bithiazolyl)-tetra-para-sulfonato-calix[4]arene (C[4]S-BTZ) were evaluated toward the human coronavirus 229E (HCoV 229E).

Synthesis and antibacterial activity of novel enolphosphate derivatives.

A new class of enolphosphates derivatives, the 1-alkenyldiphosphates, was designed and a rapid and efficient synthesis for these compounds was developed. These new molecules showed interesting in vitro antibacterial activities (MIC) against Gram-positive bacteria (Staphylococcus aureus) and Gram-negative pathogens including Pseudomonas aeruginosa and Escherichia coli.

Preparation and physicochemical characterization of amoxicillin beta-cyclodextrin complexes.

Amoxicillin (AMOX), a penicillin A, belongs to the beta-lactam family It is usually the drug of choice within the class because it is better absorbed, following oral administration, than other beta-lactam antibiotics. Its beta-lactamase degradation might be prevented by using a molecular [AMOX:beta-CD] complex. The aim of this work was to prepare complexes using two methods and then characterize interactions between AMOX and the native beta-CD.

[Time-kill curves and evolution of membrane permeability after para-guanidinoethylcalix[4]arene exposure].

Unlabelled: Three problems at the moment: multidrug-resistant bacteria, healthcare-associated infections, and decrease of active antibiotics. We have an urgent need of new antibacterials, with an innovative mechanism of action, in order to avoid too quickly bacterial resistance. The first interface between bacteria and antibiotics is the bacterial cell wall.

p-Guanidinoethyl calixarene and parent phenol derivatives exhibiting antibacterial activities. Synthesis and biological evaluation.

The tetra-para-guanidinoethyl-calix[4]arene, its distally-disubstituted ether derivatives involving 2,2'-bithiazolyl- or 2,2'-bipyridyl-methyl groups, as well as the para-guanidinoethylphenol and its analogous derivatives have been synthesized, fully characterized and evaluated as antibacterial agents towards both gram positive and gram negative reference bacteria. The simple phenolic species showed lower activity than their calixarene analogues, confirming the hypothesis that a synergistic effect should result from the spatial organization of guanidinium and heterocycles on a macrocyclic scaffold. Introduction of the bithiazole and bipyridine substituents enhanced the activity of simple phenol derivatives, reaching, for the two Staphylococcus aureus strains in particular, the values obtained for their calixarenic parents.

A new Sephadex-based method for removing microbicidal and cytotoxic residues when testing antiseptics against viruses: Experiments with a human coronavirus as a model.

The relative lack of efficient methods for evaluating antiseptic antiviral activity, together with weaknesses in the existing European Standard (i.e. NF EN 14476+A1), underlines the need to seek a new method which could allow a more precise evaluation of the antiseptic antiviral activity of chemical agents.

Cationic compounds with activity against multidrug-resistant bacteria: interest of a new compound compared with two older antiseptics, hexamidine and chlorhexidine.

Use of antiseptics and disinfectants is essential in infection control practices in hospital and other healthcare settings. In this study, the in vitro activity of a new promising compound, para-guanidinoethylcalix[4]arene (Cx1), has been evaluated in comparison with hexamidine (HX) and chlorhexidine (CHX), two older cationic antiseptics. The MICs for 69 clinical isolates comprising methicillin-resistant Staphylococcus aureus, methicillin-sensitive S.

Towards calixarene-based prodrugs: Drug release and antibacterial behaviour of a water-soluble nalidixic acid/calix[4]arene ester adduct.

A water-soluble calixarene-based heterocyclic podand incorporating a quinolone antibiotic subunit, the nalidixic acid, was synthesised and fully characterised. Its prodrug behaviour was assessed in vitro by HPLC, demonstrating the release of the tethered quinolone in model biological conditions. Microbiological studies performed on various Gram-positive and Gram-negative reference strains showed very interesting antibacterial activities.

Effective ribavirin concentration in mice brain using cyclodextrin as a drug carrier: evaluation in a measles encephalitis model.

Ribavirin (RBV) is a water-soluble synthetic nucleoside with broad spectrum antiviral properties, but it is ineffective against major viral encephalitis because of a failure to cross the blood-brain barrier (BBB). The antiviral activity of the complex ribavirin/alpha-cyclodextrin was previously demonstrated to be stronger than free ribavirin, in an in vivo model of measles virus (MV) encephalitis in mice. The role of cyclodextrin (CD) on ribavirin uptake into the brain needs to be defined.

Ursolic, oleanolic and betulinic acids: antibacterial spectra and selectivity indexes.

Ethnopharmacological Relevance: Ursolic acid (UA), oleanolic acid (OA) and betulinic acid (BA), three hydroxyl pentacyclic triterpenoic acids (HPTAs) naturally found in a large variety of vegetarian foods, medicinal herbs and plants have been investigated for antibacterial activity.

Aim Of The Study: To determine the antibacterial activity of UA, OA and BA, as well as the toxic impact on eukaryotic cells.

Materials And Methods: Minimum inhibitory concentrations were determined against five reference strains (Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923 & ATCC 29213, Enterococcus faecalis ATCC 29212 and Pseudomonas aeruginosa ATCC 27853), as well as five antibiotic-resistant clinical isolates.

Tetrazolium salts for MIC determination in microplates: why? Which salt to select? How?

We reported evaluation of a colorimetric MIC assessment for routine susceptibility testing of non-fastidious bacteria, with addition of growth indicators (INT and MTT). Our results made us postulate that the use of such indicators was unnecessary for MIC determination in routine microdilution method.

In vivo antiviral activity of ribavirin/alpha-cyclodextrin complex: evaluation on experimental measles virus encephalitis in mice.

Intracranial injection of the rodent adapted CAM/RB strain of measles virus (MV) induces encephalitis in CBA/ca mice. It has already been shown that cyclodextrins can be used as carriers to increase the antiviral activity of ribavirin (RBV) against MV in cellular model. In this study, the antiviral activity of a RBV/alpha-cyclodextrin complex has been evaluated in vivo using the above model.

[Microelectrophoresis and atomic force microscopy: new tools to explore mechanism of action of antibacterial compounds].

Microbial cell surface properties play a central role in controlling phenomena such as bacterial adhesion and biofilm formation (on stent or on prosthesis for example). The quantification of these properties and the understanding of interactions with antibacterial compounds remain difficult, in view of the complex and dynamic nature of the cell wall constituents. Various approaches, macroscopic, microscopic or molecular, have been developed.

[The Chikungunya virus].

Chikungunya virus (CHIKV), a member of the Alphavirus genus, represents a real public health problem in tropical regions of the Southeast Asia and Africa. It is transmitted to the man by Aedes mosquitoes and the illness, known as Chikungunya, is characterized by fever, eruptions and invalidating arthralgia. An increased surveillance in tropical and subtropical areas is necessary, as far as we have noticed recently the emergence of this new disease in regions where it had never existed before.

In vitro activity of para-guanidinoethylcalix[4]arene against susceptible and antibiotic-resistant Gram-negative and Gram-positive bacteria.

Objectives: Emergence of multidrug-resistant bacteria has encouraged vigorous efforts to develop antimicrobial agents with new mechanisms of action. In this study, the in vitro antibacterial activity of para-guanidinoethylcalix[4]arene was evaluated and compared with that of its constitutive monomer, para-guanidinoethylphenol. Hexamidine, a widely used antiseptic, and synthalin A, an old antidiabetic and anti-trypanosomal compound, were chosen as references.

Molecular characterization of African orthobunyaviruses.

The genus Orthobunyavirus is composed of segmented, negative-sense RNA viruses that are responsible for mild to severe human diseases. To date, no molecular studies of bunyaviruses in the genus Orthobunyavirus from central Africa have been reported, and their classification relies on serological testing. Four new primer pairs for RT-PCR amplification and sequencing of the complete genomic small (S) RNA segments of 10 orthobunyaviruses isolated from the Central African Republic and pertaining to five different serogroups have been designed and evaluated.

[Towards new antibacterial drugs. Interest of para-guanidinoethylcalix[4]arene].

We present here the results concerning the antibacterial properties evaluation of para-guanidinoethylcalix[4]arene, compared with its constitutive monomer, the para-guanidinoethylphenol, and hexamidine (Hexomédine), an antiseptic from the diamidine family widely used in therapeutic, chosen as a reference in this study for its resemblance in terms of functional groups. Antibacterial activities of those three compounds were evaluated by microdilution methods, in Mueller Hinton broth, onto 5 bacterial strains: Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 25923 & ATCC 29213 and Enterococcus faecalis ATCC 29212, according to CA-SFM and CLSI (formerly NCCLS) approved standards. In parallel, the effects of these three compounds on MRC-5 eukaryotic cell viability were evaluated with MTT assay.

Functional organisation and gain of activity: the case of the antibacterial tetra-para-guanidinoethyl-calix[4]arene.

The antibacterial activities of the para-guanidinoethylphenol and of its cyclic tetramer, the tetra-para-guanidinoethyl-calix[4]arene, have been evaluated on reference gram-positive and gram-negative bacteria. Antibiotic disk diffusion assays completed by micromethod technique were employed to determine if a synergistic effect could be expected from the spatial organisation of the monomer into its cyclic tetrameric analogue. Disk diffusion assays and microdilution experiments revealed better properties for the calixarene species, with a real and important gain of activity with regards to the monomer.

Synthesis and antibacterial activity of mechanism-based inhibitors of KDO8P synthase and DAH7P synthase.

KDO8PS (3-deoxy-D-manno-2-octulosonate-8-phosphate synthase) and DAH7PS (3-deoxy-D-arabino-2-heptulosonate-7-phosphate synthase) are attractive targets for the development of new anti-infectious agents. Both enzymes appear to proceed via a common mechanism involving the reaction of phosphoenolpyruvate (PEP) with arabinose 5-phosphate or erythrose-4-phosphate, to produce the corresponding ulosonic acids, KDO8P and DAH7P, respectively. The synthesis of new inhibitors closely related to the supposed tetrahedral intermediate substrates for the enzymes is described.

Improved antiviral activity in vitro of ribavirin against measles virus after complexation with cyclodextrins.

Despite vaccination, measles remains a burden in both developed and developing countries and complications may necessitate an efficient therapy. Measles virus (MEV) is susceptible to ribavirin (RBV), but the use of this drug is limited by its toxicity. Cyclodextrins (CDs) can form complexes with numerous molecules, improving their bioavailability and their biological properties.

In vitro antiviral efficacy of the ganciclovir complexed with beta-cyclodextrin on human cytomegalovirus clinical strains.

The toxicity of the compounds currently used in the treatment of human cytomegalovirus (HCMV) infections in immunocompromised hosts may force the treatment to be discontinued. The aim of this study was to improve the antiviral activity of ganciclovir (GCV), one the most widely used drug, by complexing it with beta-cyclodextrin. Cyclodextrins (cds) have the property to form inclusion complexes with a great number of molecules and to enhance bioavailability and biological properties of these molecules.

Effect of the complexation with cyclodextrins on the in vitro antiviral activity of ganciclovir against human cytomegalovirus.

The toxicity of the molecules currently used in the treatment of human cytomegalovirus (HCMV) in immunocompromised hosts often causes interruption of the therapy. Cyclodextrins (Cds), oligosaccharides possessing a hydrophobic cavity, have the property of forming inclusion complexes with a great number of molecules, improving their bioavailability and their biological properties. In this study, we have tested the ability of three native Cds to improve the antiviral effect of ganciclovir (GCV) on two HCMV strains: AD169, a reference susceptible strain, and RC11, a GCV resistant strain.

Influence of the fluoroquinolone ofloxacin on the intrinsic expression of multidrug resistance phenotype in HCT-8 human colon carcinoma cells.

The influence of antibiotics, particularly ofloxacin (OF), a commonly used antimicrobial fluoroquinolone, on the multidrug resistance (MDR) phenotype of the HCT-8 cell line was studied. This cell line was grown in OF containing medium for several months and the expression of the MDR phenotype was followed through the analysis of the expression and functionality of the P-glycoprotein (Pgp), the chemosensitivity to daunorubicin (DNR), and the mRNA expression of mdr-1, multidrug resistance-associated protein (MRP), and topoisomerase IIalpha and IIbeta genes. Replacement of OF by penicillin streptomycin (PS) resulted in a significant decrease in mdr-1 mRNA expression, which was found to correlate with a decrease in the expression and functionality of the Pgp.

Susceptibility of clinical strains of herpes simplex virus to three nucleoside analogues.

The susceptibility of clinical isolates of herpes simplex virus 1 (HSV1) (58 strains) and 2 (HSV2) (17 strains) from the Centre Hospitalier et Universitaire de Nancy to three nucleoside analogues was compared by the dye uptake method. As expected, all strains of HSV2 were resistant to brovavir or sorivudine. Aciclovir and penciclovir activities were comparable; 2 strains of HSV1 were resistant to these two compounds.