Sinteza i antimikotsko djelovanje 4-supstituiranih 3-(tiofen-2-il-metil)- Δ2-1,2,4-triazolin-5-tiona

In the reaction of hydrazide of thiophene-2-acetic acid (1) with isothiocyanates, the respective thiosemicarbazides 2a-g were obtained. Further cyclization with 2% NaOH led to formation of 4-substituted-3-(thiophene-2-yl-methyl)-delta2-1,2,4-triazoline-5-thiones (3a-g). These compounds showed promising antimycotic activity.Rekacijom hidrazida tiofen-2-octene kiseline (1) s izotiocijanatima sintetizirani su odgovarajući tiosemikarbazidi (2a-2g), a njihovom ciklizacijom u 2% NaOH 4-supstituirani 3-(tiofen-2-il-metil)-Δ2-1,2,4-triazolin-5-tioni (3a-3g). Ti spojevi su potencijalni antimikotici

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.This research was supported by the Ministry of Science and Higher Education under Iuventus Plus grant No. IP2014 037473. Tomasz Plech is a recipient of the Fellowship for Young Researchers with Outstanding Scientific Achievements from the Medical University of Lublin (Lublin, Poland)

Antibacterial Activity of Fluorobenzoylthiosemicarbazides and Their Cyclic Analogues with 1,2,4-Triazole Scaffold

The development of drug-resistant bacteria is currently one of the major challenges in medicine. Therefore, the discovery of novel lead structures for the design of antibacterial drugs is urgently needed. In this structure–activity relationship study, a library of ortho-, meta-, and para-fluorobenzoylthiosemicarbazides, and their cyclic analogues with 1,2,4-triazole scaffold, was created and tested for antibacterial activity against Gram-positive bacteria strains. While all tested 1,2,4-triazoles were devoid of potent activity, the antibacterial response of the thiosemicarbazides was highly dependent on substitution pattern at the N4 aryl position. The optimum activity for these compounds was found for trifluoromethyl derivatives such as 15a, 15b, and 16b, which were active against both the reference strains panel, and pathogenic methicillin-sensitive and methicillin-resistant Staphylococcus aureus clinical isolates at minimal inhibitory concentrations (MICs) ranging from 7.82 to 31.25 μg/mL. Based on the binding affinities obtained from docking, the conclusion can be reached that fluorobenzoylthiosemicarbazides can be considered as potential allosteric d-alanyl-d-alanine ligase inhibitors

Upper respiratory tract microbiota in health and disease – a minireview

A most common infection is that the upper respiratory tract. The human body is inhabited by millions of microorganisms, most of which enable the proper functioning of some systems and constitute a barrier protecting against harmful external factors. Due to the continuous contact of the upper airway microbiota with the external environment, it may seem to be extremely unstable and very diverse. A number of studies have been conducted that have assessed the effect of various factors on the composition of the upper respiratory tract microbiota. This paper presents a literature analysis which showed that the anatomical area is rich in terms of the microbiota that forms it, and despite the constant changes in many parameters, including physical – very stable

Synthesis and antibacterial activity of new (2,4-dioxothiazolidin-5-yl/ylidene)acetic acid derivatives with thiazolidine-2,4-dione, rhodanine and 2-thiohydantoin moieties

A series of new (2,4-dioxothiazolidin-5-yl/ylidene)acetic acid derivatives with thiazolidine-2,4-dione, rhodanine and 2-thiohydantoin moiety (28–65) were synthesized by the reaction of (2,4-dioxothiazolidin-5-yl/ylidene)acetic acid chlorides with 5-(hydroxybenzylidene) thiazolidine-2,4-dione, rhodanine and 2-thiohydantoin derivatives. Obtained compounds (28–65) were tested on reference strains of Gram-positive bacteria and ones of the Gram-negative bacteria. The antibacterial activity of target compounds was determined by broth microdilution method. These derivatives showed antibacterial activity generally against Gram-positive bacterial strains. Most active compounds possess MIC = 3.91 mg/L. Our results suggest that presence of electron-withdrawing substituent at phenyl ring is favorable while geometry of molecule does not play important role in antibacterial response. It was confirmed the lack of direct influence of substitution pattern at phenyl ring on antibacterial activity of closely related compounds of series 1–3. The antibacterial activity of some compounds was similar or higher than the activity of commonly used reference drugs such as oxacillin and cefuroxime. Keywords: Thiazolidine-2,4-dione, Rhodanine, 2-Thiohydantoin, Antibacterial activit

Haemophilus influenzae and Haemophilus parainfluenzae occurrence in the ear effusion in pediatric patients prone to recurrent respiratory tract infections (RRTI) and with otitis media with effusion (OME)

Introduction.Haemophilus influenzae and Haemophilus parainfluenzae are known as human-restricted respiratory microbiota representatives. The aim of the present paper was to assay haemophili prevalence in middle ear effusion specimens in pediatric patients with otitis media with effusion (OME)

Influence of Thiazolidine-2,4-Dione Derivatives with Azolidine or Thiosemicarbazone Moieties on Haemophilus spp. Planktonic or Biofilm-Forming Cells

Biofilm, naturally formed by microorganisms as integrated surface-bound communities, is one of the reasons for the development of antimicrobial resistance. Haemophilus spp. are common and representative opportunistic Gram-negative rods forming from the upper respiratory tract microbiota. The aim of this paper was to evaluate the influence of thiazolidine-2,4-dionebased azolidine and chlorophenylthiosemicarbazone hybrids against both planktonic and biofilm-forming Haemophilus spp. cells. The in vitro activity against planktonic and biofilm-forming cells of the tested compounds were evaluated by using the broth microdilution method. These activities were detected against reference and clinical strains of Haemophilus spp. on the basis of MICs (minimal inhibitory concentrations) and MBICs (minimal biofilm inhibitory concentrations). In addition, anti-adhesive properties of these compounds were examined. The target compounds showed potential activity against planktonic cells with MIC = 62.5–500 mg/L and biofilm-forming cells with MBIC = 62.5–1000 mg/L. The observed anti-adhesive properties of the tested compounds were reversible during long-term incubation in a lower concentration of compounds

Phenotypic diversity of Haemophilus influenzae and Haemophilus parainfluenzae isolates depending on origin and health condition

Background. Haemophili are common human microbiota representatives. The aim of our study was to investigate a diversity of Haemophilus spp. isolates selected from clinical specimens on the basis of biochemical characteristics, biotypes distribution, protein profiles and antimicrobial resistance. Results. A total of 893/1025 (87%) of haemophili isolates were identified: 260/1025 (25%) as H. influenzae and 633/1025 (62%) as H. parainfluenzae. Moreover, a group of 107/1025 (10%) isolates without species identification (with e.g. abnormal numerical profile) was described as Haemophilus spp. Within the H. influenzae isolates, biotypes II and III were in a great majority (92/893; 10%, each), whereas among H. parainfluenzae, the most commonly occurring was biotype I and II (301/893, 34% and 178/893, 20%, respectively). A similar prevalence of biotypes was obtained regardless of the patient’s age or health condition or the type of specimen. A production of beta-lactamases was shown in 46/893 (5%) haemophili, both H. influenzae (13/46, 28%) and H. parainfluenzae (33/46, 72%) isolates. On the basis of haemophili biochemical characteristics, the cluster analysis using the UPGMA method demonstrated a high degree of phenotypic similarity due to a small distances between isolates taken from both unhealthy children and adults. Conclusion. Based on biochemical characteristics, about 90% of haemophili clinical isolates representing human-specific respiratory microbiota were positively identified as H. influenzae and H. parainfluenzae. The same differences in biotypes and antimicrobial resistance among isolates selected from healthy people or from patients with chronic and recurrent diseases were detected

Inhibitory effect of N-ethyl-3-amino-5-oxo-4-phenyl-2,5-dihydro-1H-pyrazole-1-carbothioamide on Haemophilus spp. planktonic or biofilm-forming cells

During this study, we have investigated in vitro activity of N-substituted-3-amino-5-oxo-4-phenyl-2,5-dihydro-1H-pyrazole-1-carbothioamide derivatives with N-ethyl, N-(4-metoxyphenyl) and N-cyclohexyl substituents against Gram-negative Haemophilus influenzae and H. parainfluenzae bacteria. A spectrophotometric assay was used in order to determine the bacterial growth and biofilm formation using a microtiter plate to estimate minimal inhibitory concentration (MIC) and minimal biofilm inhibitory concentration (MBIC). Among the tested N-substituted pyrazole derivatives, only N-ethyl-3-amino-5-oxo-4-phenyl-2,5-dihydro-1H-pyrazole-1-carbothioamide showed a significant in vitro activity against both planktonic cells of H. parainfluenzae (MIC = 0.49–31.25 μg ml(−1)) and H. influenzae (MIC = 0.24–31.25 μg ml(−1)) as well as biofilm-forming cells of H. parainfluenzae (MBIC = 0.24–31.25 μg ml(−1)) and H. influenzae (MBIC = 0.49 to ≥31.25 μg ml(−1)). The pyrazole compound exerted higher inhibitory effect both on the growth of planktonic cells and biofilm formation by penicillinase-positive and penicillinase-negative isolates of H. parainfluenzae than the activity of commonly used antibiotics such as ampicillin. No cytotoxicity of the tested compound in vitro at concentrations used was found. The tested pyrazole N-ethyl derivative could be considered as a compound for the design of agents active against both pathogenic H. influenzae and opportunistic H. parainfluenzae, showing also anti-biofilm activity. This appears important because biofilms are determinants of bacterial persistence in long-term and recurrent infections recalcitrant to standard therapy