Łukasz Świątek

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.

Synthesis and antiviral activity of 1-(1,3-disubstitutedimidazolidyn-2-ylidene)-3-ethoxycarbonylmethylurea derivatives

Abstract Novel 1-(1,3-disubstituted-imidazolidyn-2-ylidene)-3-ethoxycarbonylmethylurea derivatives (3a–3j) were obtained from appropriate 1-aryl-3-arylsulfonyl-1H-imidazolidine-2-imines (1a–1j) and ethyl isocyanatoacetate (2), which were subjected to condensation. Seven compounds were tested for their antiviral activity against HSV-1 and CVB3 viruses. Among the tested compounds, 3c was found to be active against HSV-1, proving that 4-methoxy substituent as R and 4-methyl substituent as R1 are most beneficial for activity against this virus. Furthermore, 3e and 3g were active against CVB3, which demonstrated that both 4-methyl and 4-chloro substitution is tolerated as R1, whereas 4-chloro and 2-methoxy substituents are best as R. It was also shown that the active compounds are characterized by relatively big surface area, small ovality, and greatest HOMO and LUMO energies in comparison to the rest of the compounds.

Design, synthesis, structure elucidation and in vitro antiviral and antimicrobial evaluation

In this study, we described the synthesis of the derivatives of thiosemicarbazide, dicarboximide, 1,2,4-triazole-5-thione and 4-oxo-1,3-thiazolidine. Two different dicarboxylic acid anhydrides reacted with 4-substituted-3-thiosemicarbazide, and derivatives of thiosemicarbazide and dicarboximide were obtained. Next, cyclization reaction of dicarboximide derivatives in alkaline media was used to prepare 1,2,4-triazole-5-thione. The 4-oxo-1,3-thiazolidine was synthesized by the reaction of dicarboximide with ethyl bromoacetate. All obtained derivatives were analysed by 1H and 13C NMR spectra, and for one compound, the X-ray crystallography was done. Antimicrobial, antiviral and in vitro evaluations of cytotoxicity were examined. According to the preliminary antiviral screening, compounds 3 and 4 presented the antiviral activity against HSV-1 and CVB3. Additionally, compound 3 shows selective in vitro toxic effect against human epithelial cells FaDu, without affecting normal animal cell line (Vero). The same derivatives 3 and 4 also displayed a wide spectrum of antimicrobial activity against reference microorganisms and indicated both antibacterial and antifungal potential activities.

Chemical profile, antioxidant activity and cytotoxic effect of extract from leaves of Erythrochiton brasiliensis Nees & Mart. from different regions of Europe

Abstract The total phenolic content (TPC), total tannin content (TTC) and total flavonoid content (TFC) as well as the antioxidant activity and the cytotoxic effect of the extract from leaves of Erythrochiton brasiliensis Nees & Mart. (Rutaceae) were evaluated. Raw material was collected in different European botanical gardens. Statistical analysis revealed a clear grouping of populations according to their climatic zone. The average TPC, TTC and TFC in tested samples were 35.92 (± 7.11) mg GAE·g–1 DW, 14.98 (± 4.08) mg PyE·g–1 DW and 2.92 (± 0.76) mg QuE·g–1 DW, respectively. The scavenged DPPH and Trolox equivalents determined by EPR spectroscopy were 1.23–4.14 and 0.50–1.44 mmol·g–1 of dry extract, respectively. Thirteen compounds (derivatives of bezoic acid acid and trans-cinnammic acid) were identified in the samples. The flavonoid vitexin was also present as the major component in three investigated samples. The in vitro cytotoxicity test of the extract on Vero cells provided IC50 and IC10 values of 175.6 and 72.5 μg·mL–1, respectively. Incubation of samples with HHV-1 infected Vero cells had no effect on the occurrence of cytopathic effect.

Lithium as a prooxidant? A possible protective role of selenium – in vitro study

INTRODUCTION AND OBJECTIVE Lithium is used in medicine but its application may cause diverse side effects. Selenium has been found to show protective properties against negative influence of different harmful factors. This study was aimed at evaluating the influence of non-toxic dose of lithium on antioxidant parameters in FaDu (ATCC HTB-43) and Vero (ECACC No. 84113001) cell lines as well as the possible protective effect of non-toxic concentration of sodium selenite. MATERIAL AND METHODS The cells were subjected to 0.17 mmol/L of Li2CO3 and/or 2.9 µmol/L of Na2SeO3 · 5H2O for Vero as well as 0.47 mmol/L of Li2CO3 and/or 3.0 µmol/L of Na2SeO3 · 5H2O for FaDu cells. The incubation was continued for the subsequent 72 h. In the cells total antioxidant status (TAS) values, activities of antioxidant enzymes - superoxide dismutase (SOD) and glutathione peroxidase (GPx) as well as the reduced glutathione concentration (GSH) were determined. RESULTS AND CONCLUSION In Vero cells lithium decreased all studied parameters, particularly GPx. Selenium co-treatment showed a distinct protective effect. In FaDu cells the similar effect was observed only in case of GSH. The results point to differences in action of lithium and selenium in physiological and pathological state. As long-term lithium therapy is applied in psychiatric patients the results regarding Vero line let suggest that selenium might be considered as an adjuvant alleviating side effects of Li-treatment.

Synthesis, antiviral activity and structure–activity relationship of 1-(1-aryl-4,5-dihydro-1H-imidazoline)-3-chlorosulfonylureas and products of their cyclization

Abstract Novel 1-(1-aryl-4,5dihydro-1H-imidazoline)-3-chlorosulfonylourea derivatives 3a–3f were synthesized in the reaction of 1-aryl-4,5-dihydro-1H-imidazol-2-amines with chlorosulfonyl isocyanate. The second series of compounds 4a–4f was prepared from the respective 1-(1-aryl-4,5-dihydro-1H-imidazoline)-3-chlorsulfonylureas 3a–3f and 1,1′-carbonyldiimidazole (CDI). The selected compounds were tested for their activity against Herpes simplex virus and coxsackievirus B3 (CVB3). It was determined that three derivatives, i.e 3d, 4a and 4d are active against Herpes simplex virus (HSV-1). Compounds 3d and 4c are active against CVB3. Their favorable activity can be primarily attributed to their low lipophilicity values. Moreover, the lack of substituent in the phenyl moiety or 4-methoxy substitution can be considered as the most beneficial for the antiviral activity.