Urszula Kosikowska

Synthesis and antimicrobial activity of thiosemicarbazides, s-triazoles and their Mannich bases bearing 3-chlorophenyl moiety

A fast and efficient synthesis of some 1,4-disubstituted thiosemicarbazide derivatives is described. The reaction of 3-chlorobenzoic acid hydrazide with various aryl isothiocyanates gave thiosemicarbazide derivatives (1-11) in good yield. The cyclization of compounds (1-11) in the presence of 2% NaOH resulted in the formation of compounds (12-22) containing the 1,2,4-triazole ring. A series of new Mannich bases (23-33) related to the structure of 1,2,4-triazole has been also synthesized. All of these compounds were tested for their in vitro antibacterial activity against the reference strains of aerobic bacteria - 6 Gram-positive and 3 Gram-negative ones; 12 Staphylococcus aureus clinical isolates were also examined. An attempt was made to clarify the influence of the nature/position of substituents on antibacterial activity of compounds described.

Synthesis and in vitro activity of 1,2,4-triazole-ciprofloxacin hybrids against drug-susceptible and drug-resistant bacteria

A series of novel 1,2,4-triazole-ciprofloxacin hybrids was designed, synthesised and evaluated in vitro against drug-susceptible and drug-resistant bacteria. A significant part of the compounds obtained showed antibacterial activity higher than the activity of ciprofloxacin, both towards Gram-positive and Gram-negative species. Despite relatively small number of synthesised derivatives, it was possible to observe important dependences between their structure and activity.

Search for factors affecting antibacterial activity and toxicity of 1,2,4-triazole-ciprofloxacin hybrids.

A series of 1,2,4-triazole-based compounds was designed as potential antibacterial agents using molecular hybridization approach. The target compounds (23-44) were synthesized by Mannich reaction of 1,2,4-triazole-3-thione derivatives with ciprofloxacin (CPX) and formaldehyde. Their potent antibacterial effect on Gram-positive bacteria was accompanied by similarly strong activity against Gram-negative strains. The toxicity of the CPX-triazole hybrids for bacterial cells was even up to 18930 times higher than the toxicity for human cells. The results of enzymatic studies showed that the antibacterial activity of the CPX-triazole hybrids is not dependent solely on the degree of their affinity to DNA gyrase and topoisomerase IV.

Determination of the Primary Molecular Target of 1,2,4-Triazole-Ciprofloxacin Hybrids

We have synthesized and examined the antibacterial activity, toxicity and affinity towards bacterial type II topoisomerases of a series of 1,2,4-triazole-ciprofloxacin hybrids. A number of these compounds displayed enhanced activity against Gram-positive and Gram-negative bacteria when compared to ciprofloxacin. The toxic concentrations of the obtained derivatives, evaluated on HEK-293 cells using MTT assay, were much higher than concentrations required to produce antibacterial effect. Finally, the results of enzymatic studies showed that the analyzed compounds demonstrated other preferences as regards primary and secondary molecular targets than ciprofloxacin.

Reaction of hydrazide of (tetrazol-5-yl)acetic acid with isothiocyanates and antimicrobial investigations of newly-obtained compounds

In the reaction of hydrazide of (tetrazol-5-yl)acetic acid (1) with isothiocyanate the respective thiosemicarbazide derivatives 2 were obtained. Further cyclization with 2% NaOH led to the formation of 3-[(tetrazol-5-yl)-methyl]-4-substituted-1,2,4-triazoline-5-thione 3. The structures of all new products were confirmed by analytical and spectroscopic methods. Five compounds were screened for their in vitro activity against some species of aerobic bacteria and fungi. Derivatives of 1,2,4-triazoline-5-thione can exist in two major tautomeric forms; thiole and thione. We have established experimentally that all obtained compounds 3, were in the thione form. Geometry optimization of tautomeric forms of 3c and 3f was carried out.

Microbiologically active Mannich bases derived from 1,2,4-triazoles. The effect of C-5 substituent on antibacterial activity

Our research proved that chemical character of the C-5 substituent significantly determines the antibacterial activity of the Mannich bases derived from 4,5-disubstituted 1,2,4-triazole-3-thiones. This activity was considerably increased by an introduction of a chlorine atom to the phenyl ring. The obtained compounds were particularly active against opportunistic bacteria (Bacillus subtilis and Bacilluscereus). The antibacterial activity of some Mannich bases was similar or higher than the activity of commonly used antibiotics such as ampicillin and cefuroxime.

Antimicrobial activity and total content of polyphenols of Rheum L. species growing in Poland

In the crude ethanol extracts obtained from the rhizome and roots of Rheum palmatum L., Rheum undulatum L. and Rheum rhaponticum L. growing in Poland concentration of polyphenols ranged from 46.11 to 76.45 mg/g. Concentration of tannins ranged from 7.07% to 8.67%, while anthracene derivatives and anthraquinones varied by species - R. palmatum measured 36.3 and 34 mg/g, while R. undulatum or R. rhaponticum did not exceed 20.4 and 18.1 or 19.8 mg/g and 16.6 mg/g, respectively. Using a broth microdilution method it was found that all of the Rheum spp. extracts were more active against reference strains of Gram-positive bacteria (Staphylococcus spp.) than against those of Gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis). The strongest inhibitory effect against Staphylococcus spp. was exerted by R. undulatum extract with MIC = 125–250 μg/mL. The moderate in vitro antibacterial activity of R. undulatum suggests that this plant, often used in the European cuisine to improve flavour, may be also important and useful as an alternative or auxiliary medicine remedy in the treatment of uncomplicated superficial infections caused especially by clinically important staphylococci, potentially pathogenic S. aureus or opportunistic S. epidermidis.

Nasopharyngeal and Adenoid Colonization by Haemophilus influenzae and Haemophilus parainfluenzae in Children Undergoing Adenoidectomy and the Ability of Bacterial Isolates to Biofilm Production.

AbstractHaemophili are pathogenic or opportunistic bacteria often colonizing the upper respiratory tract mucosa. The prevalence of Haemophilus influenzae (with serotypes distribution), and H. parainfluenzae in the nasopharynx and/or the adenoid core in children with recurrent pharyngotonsillitis undergoing adenoidectomy was assessed. Haemophili isolates were investigated for their ability to biofilm production.Nasopharyngeal swabs and the adenoid core were collected from 164 children who underwent adenoidectomy (2–5 years old). Bacteria were identified by the standard methods. Serotyping of H. influenzae was performed using polyclonal and monoclonal antisera. Biofilm formation was detected spectrophotometrically using 96-well microplates and 0.1% crystal violet.Ninety seven percent (159/164) children who underwent adenoidectomy were colonized by Haemophilus spp. The adenoid core was colonized in 99.4% (158/159) children, whereas the nasopharynx in 47.2% (75/159) children (P < 0.0001). In 32% (51/159) children only encapsulated (typeable) isolates of H. influenzae were identified, in 22.6% (36/159) children only (nonencapsulated) H. influenzae NTHi (nonencapsulated) isolates were present, whereas 7.5% (12/159) children were colonized by both types. 14.5% (23/159) children were colonized by untypeable (rough) H. influenzae. In 22% (35/159) children H. influenzae serotype d was isolated. Totally, 192 isolates of H. influenzae, 96 isolates of H. parainfluenzae and 14 isolates of other Haemophilus spp. were selected. In 20.1% (32/159) children 2 or 3 phenotypically different isolates of the same species (H. influenzae or H. parainfluenzae) or serotypes (H. influenzae) were identified in 1 child. 67.2% (129/192) isolates of H. influenzae, 56.3% (54/96) isolates of H. parainfluenzae and 85.7% (12/14) isolates of other Haemophilus spp. were positive for biofilm production. Statistically significant differences (P = 0.0029) among H. parainfluenzae biofilmproducers and nonproducers in the adenoid core and the nasopharynx were detected.H. influenzae and H. parainfluenzae carriage rate was comparatively higher in the adenoid core than that in the nasopharynx in children undergoing adenoidectomy, suggesting that their involvement in chronic adenoiditis. The growth in the biofilm seems to be an important feature of haemophili colonizing the upper respiratory tract responsible for their persistence.

Synthesis, Structure and Antibacterial Evaluation of Some N-substituted 3-amino-5-hydroxy-4-phenyl-1H-pyrazole-1-carboxamides

N-substituted 3-amino-5-hydroxy-4-phenyl-1H-pyrazole-1-carboxamide derivatives have been prepared by heterocyclization of 1-cyanophenyl acetic acid hydrazide with isocyanates. Representative compounds were evaluated as potential antimicrobial agents. The most promising compound in this series, the N-(1-naphthyl)-3-amino-5-hydroxy-4-phenyl-1H-pyrazole-1-carboxamide 2f, was the most effective against the reference strains of pathogenic S. aureus ATCC 25923 and S. aureus ATCC 6538 or opportunistic S. epidermidis ATCC 12228 with MIC value of 7.81 μg/ml and against the other gram-positive species with MIC values 15.63-31.25 μg/ml. This compound also showed high activity against clinical isolates of MSSA (methicillin-sensitive Staphylococcus aureus) with MIC of 0.98-31.25 μg/ml and MRSA (methicillin-resistant Staphylococcus aureus) with MIC of 1.96-7.81 μg/ml.

Synthesis and Antimicrobial Evaluation of New Schiff Base Hydrazones Bearing 1,2,4-Triazole Moiety

GRAPHICAL ABSTRACT Abstract This study presents the synthesis and spectral analysis of new Schiff base hydrazone derivatives. New compounds were prepared by the reaction of [(4-phenyl-5-substituted-4H-1,2,4-triazol-3-yl)sulfanyl] acetohydrazide with various aldehydes. The structures of the prepared compounds were confirmed by means of 1H NMR, 13C NMR, and elemental analyses. All synthesized compounds were screened for their in vitro antimicrobial activity by using the agar dilution technique against four reference strains of Gram-positive and Gram-negative bacteria and 12 yeasts belonging to Candida spp.