New Antimicrobial Approaches: Reuse of Old Drugs.

The global situation of antibiotic resistance and the reduction of investments in antibiotics research by the pharmaceutical industry suggest the need for specific cost-effective approaches in order to identify drugs for the therapy of many microbial infections. Among the viable alternative anti-infective compounds, drug repurposing, i.e.

Recent updates and perspectives on leishmaniasis.

Leishmaniasis is a neglected vector-borne tropical infection considered to be a disease of the poor. Concentrated in poverty-stricken countries within Southeast Asia, East Africa, and Latin America, it is also endemic in several Mediterranean countries. The management of the heterogeneous syndromes determined by parasites belonging to the genus Leishmania is particularly difficult in developed, non-endemic countries owing to the unfamiliarity of physicians with clinical symptoms, diagnostic possibilities, and available treatment options.

New perspectives in the management of Pseudomonas aeruginosa infections.

Infections with Pseudomonas aeruginosa are a major health problem, especially for immune-compromised and cystic fibrosis patients, owing to the particular drug resistance of the microorganism. The aim of this review is to provide recent insights into strategies under investigation for prevention and therapy of these infections. In this survey, the approach directed against bacterial biofilm formation and quorum-sensing systems was focused, along with the evaluation of the treatment with bacteriophages.

Novel approaches for the design and discovery of quorum-sensing inhibitors.

Introduction: The spread of antibiotic resistance, together with the lack of antibiotics based on novel molecular scaffolds, marks the so-called 'post-antibiotic era'. Interference with bacterial virulence has emerged as an attractive approach among the current potential strategies for developing new anti-infective drugs. Furthermore, the discovery that virulence gene expression is mostly regulated by quorum sensing (QS) has raised a lot of interest and prompted a lot of research aimed at finding inhibitors of this mechanism.

A strange gingival swelling in an Italian child: a case of oral myiasis.

Oral myiasis is a condition in which tissues of the oral cavity are invaded by the larvae of flies. It is a rare disease in humans, often associated with very poor dental and oral hygiene. In children the main predisposing factors are incompetent lips, thumb sucking habits and continuous mouth breathing.

Novel avenues for Clostridium difficile infection drug discovery.

Introduction: Clostridium difficile is the etiologic agent of nosocomial and community-acquired diarrhea associated with exposure to antibiotics that disrupt the normal colonic flora. As antibacterials currently used for primary C. difficile infections favor recurrences, new agents able to neutralize the bacterium without affecting the gut microbiota are badly needed.

New chemotherapeutic strategies against malaria, leishmaniasis and trypanosomiases.

Due to the persistent lack of suitable vaccines, chemotherapy remains the only option for the treatment of patients infected by protozoan parasites. However, most available antiparasitic drugs have serious disadvantages, ranging from high cost and poor compliance to high toxicity and rapid induction of resistance. In recent decades basic research laboratories identified a considerable number of promising new molecules, but their development has not been pursued in depth by pharmaceutical firms because of poor prospects of economic return.

Plant-derived antimicrobial compounds: alternatives to antibiotics.

The increasing incidence of drug-resistant pathogens has drawn the attention of the pharmaceutical and scientific communities towards studies on the potential antimicrobial activity of plant-derived substances, an untapped source of antimicrobial chemotypes, which are used in traditional medicine in different countries. The aim of this review is to provide recent insights regarding the possibilities of the most important natural antimicrobial compounds derived from plant sources containing a wide variety of secondary metabolites, which are useful as alternative strategies to control infectious diseases. This review will focus on natural plant products as a useful source of antimicrobial molecules, active in particular, on bacteria and fungi.

New antimicrobial frontiers.

New antimicrobials able to counteract bacterial resistance are needed to maintain the control of infectious diseases. The last 40 years have seen the systematic tailoring and refinement of previously identified antibiotics, to produce a multitude of semi-synthetic derivatives that share their mechanism of action with the original molecules. The major limit of this approach is the emergence of multi- and cross-resistant bacterial strains, favoured by the selective pressure inherent to the targeting of specific enzymes.

Current developments in the therapy of protozoan infections.

Protozoan parasites cause serious human and zoonotic infections, including life-threatening diseases such as malaria, African and American trypanosomiasis, and leishmaniasis. These diseases are no more common in the developed world, but together they still threaten about 40% of the world population (WHO estimates). Mortality and morbidity are high in developing countries, and the lack of vaccines makes chemotherapy the only suitable option.

Analysis of Escherichia coli isolated from patients affected by Crohn's disease.

The etiopathogenesis of Crohn's disease (CD) is still controversial: several genetic, immunologic, and environmental factors, including some bacteria, have been implicated. This study has been devised to assess the involvement of Escherichia coli in CD. Seven E.

C-hexaphenyl-substituted trianglamine as a chiral solvating agent for carboxylic acids.

Chiral hexaazamacrocycles with a trianglamine structure and C(3)-symmetry, containing six ring substituents and twelve stereocenters have been tested as chiral solvating agents (CSAs) for α-substituted carboxylic acids. Excellent results have been obtained with a hexaphenyl-substituted macrocycle. The optimal ratio between the macrocycle and racemic acid, allowing for baseline separation of the enantiomers' signals in the (1)H NMR spectrum, was dependent on the type of acid, in particular on its degree of acidity.

Pyrrole macrocyclic ligands for Cu-catalyzed asymmetric Henry reactions.

New chiral perazamacrocycles containing four pyrrole rings have been synthesized by the [2+2] condensation of (R,R)-diaminocyclohexane and 5,5'-(alkane-2,2-diyl)bis(1H-pyrrole-2-carbaldehydes). These macrocycles, differing for the alkyl/aryl meso-substituents, were used as ligands in the copper-catalyzed Henry reactions of aromatic and aliphatic aldehydes with nitroalkanes. In the optimized experimental conditions, the condensations of nitromethane and aromatic and aliphatic aldehydes in the presence of catalytic amounts of copper diacetate and methyl-substituted macrocyclic ligand (2:1 ratio) in ethanol at room temperature provided products often with high enantiomeric excesses (up to 95% ee).

Surveillance of methicillin-resistant Staphylococcus aureus isolated in Torino (northwest Italy).

Nosocomial infections by methicillin-resistant Staphylococcus aureus (MRSA) are an increasing cause of morbidity and mortality. Recently, a worldwide increase of community-acquired MRSA infections has also been recorded. The purpose of this study was to assess the frequency of MRSA isolation from in- and outpatients admitted to an academic teaching hospital near Torino (northwest Italy) in 1 year and to characterize 90 clinical isolates of MRSA collected in the same period.

Asymmetric synthesis of 3,4-diaminocyclohexanol and endo-7-azabicyclo[2.2.1]heptan-2-amine.

Hydroboration of (1R,2R)-bis[(S)-1-phenylethylamino]cyclohex-4-ene and its derivatives with several borane reagents gave diastereomeric mixtures of the 3,4-diaminocyclohexanol derivatives. Cyclization of the prevalent diastereomer with the R configuration of the newly formed stereocenter under Mitsunobu conditions, followed by reductive removal of the N-substituents, gave the optically pure endo-7-azabicyclo[2.2.

In vitro activity of dermaseptin S1 derivatives against genital pathogens.

The aim of this study was to evaluate the biological activity of nine dermaseptin-S1 (DRS-S1) derivatives (synthesized by solid-phase methods and purified) against different pathogens causing genital infections (Trichomonas vaginalis, Herpes simplex virus, Papillomavirus). The in vitro activity on T. vaginalis was determined by counting the protozoon in a hemocytometer after vital staining with trypan blue; antiviral activity of the compounds was tested on monolayers of Vero cells for Herpes simplex virus-1 (GFP) and on 293TT cells for human papillomavirus (HPV-16) pseudovirions (GFP).

Stereoselective synthesis of ring C-hexasubstituted trianglamines.

The addition of organolithium reagents to the trianglimine derived from (R,R)-1,2-diaminocyclohexane and terephthalaldehyde gave the corresponding trianglamine with complete stereocontrol and the R configuration of all six newly formed stereocenters. The structure of the hexaphenyl-substituted macrocycle was determined by X-ray crystallographic study. The new trianglamines were tested as ligands in enantioselective catalytic reactions.

The post-antibiotic era: promising developments in the therapy of infectious diseases.

An overview of investigational antibiotics highlights that antimicrobial drug development is slower than the emergence and spread of resistant strains. In the last three decades only two antibiotics belonging to truly new classes have been introduced into the market, i.e.

Catalytic hydrogenation of meso-octamethylporphyrinogen (calix[4]pyrrole).

Hydrogenation of meso-octamethylporphyrinogen (calix[4]pyrrole) with a number of heterogeneous catalysts under different experimental conditions has been investigated. GC-MS analyses of the reaction mixtures showed the formation of one to four products in low to moderate yields: three of them were diastereoisomers of the product derived from half-hydrogenation of the substrate, and displayed alternating pyrrolidine and pyrrole rings, while the fourth was the all-cis saturated product. An acidic medium was necessary to achieve hydrogenation.

In vitro compared activity of telithromycin and azithromycin against northwest Italian isolates of Streptococcus pyogenes and Streptococcus pneumoniae with different erythromycin susceptibility.

Aims: This study compared the in vitro activity of telithromycin with that of azithromycin against 438 Streptococcus pyogenes and 198 Streptococcus pneumoniae, isolated over the period 2005-2007 from specimens of different human origin obtained in three Piemonte Region's hospitals.

Methods And Results: The determination of antimicrobial activity was evaluated by the microdilution broth method and the erythromycin-resistant (Ery-R) phenotypes by the triple-disc test. Exactly 78.

Achromobacter xylosoxidans respiratory tract infections in cystic fibrosis patients.

Achromobacter xylosoxidans is a ubiquitous Gram-negative non-fermenting rod, recently characterized as an emerging pathogen in cystic fibrosis (CF) patients. Its pathogenic potential and prevalent transmission routes are still unclear. This study investigated the PFGE genetic pattern and antimicrobial resistance profile of 42 A.

Asymmetric synthesis of 8-aminoindolizidine from chiral 2-pyrroleimines.

1-Allyl-2-pyrroleimines obtained from (S)-valinol and (S)-phenylglycinol underwent highly diastereoselective addition of allylmagnesium chloride, used in excess amounts, to give the corresponding secondary amines with concomitant allyl to (Z)-1-propenyl isomerization of the 1-pyrrole substituent. Transformation of the 2-amino alcohol moiety to an oxazolidinone, or its cleavage and subsequent N-protection, followed by ring-closing metathesis of the two alkene groups gave the unsaturated bicyclic compound. Full hydrogenation of the alkene function and the aromatic rings afforded the indolizidine derivative as a mixture of two or three diastereomers with a ratio which was dependent on the nature of both the N-substituent and the catalyst.

Synthesis and antimicrobial activity of dermaseptin S1 analogues.

Dermaseptins are peptides found in the skin secretions of Phyllomedusinae frogs. These peptides exert lytic action on some microorganisms without substantial haemolysis. In an attempt to understand the antimicrobial activity of these peptides we designed several dermaseptin S1 (ALWKTMLKKLGTMALHAGKAALGAAADTISQGTQ) (DS1) analogues.

Phenotypic and genotypic characterization of Pseudomonas aeruginosa from cystic fibrosis patients.

Pseudomonas aeruginosa accounts for about one half of all pulmonary infections of cystic fibrosis (CF) patients. In this study, we analyzed 135 P. aeruginosa strains isolated from the expectorations of 55 CF adult patients attending a CF referral center over a period of five years.