Regioselective synthesis of new 2-(E)-cyano(oxazolidin-2-ylidene)thiazoles

Reaction of 2-(oxazolidin-2-ylidene)malononitrile (1) with phosphorus pentasulfide gave the corresponding thioamide derivative (2a) in a regioselective manner. Reaction of this compound with several α-bromocarbonyl compounds gave new 2-(E)-cyano(oxazolidin-2-ylidene)thiazoles (3a-g). The chemical structures of novel compounds were confirmed by 1H NMR, elemental analysis, FT-IR spectrometry and mass spectrophotometric analyses

Synthesis, physical characterization, antifungal and antibacterial activity of oleic acid-capped nanomagnetite and cobalt-doped nanomagnetite

Nanoparticles, 10-14 nm, consisting of either Fe3O4 or Co0.2Fe2.8O4 stabilized with oleic acid, were prepared using solution combustion. Their structural and magnetic properties were examined using X-ray diffractometry, scanning electron microscopy, vibrating sample magnetometry, and Fourier-transform infrared spectroscopy. The properties of both sets of materials are similar except the cobalt-doped particles are considerably less magnetic. The in vitro inhibitory activities of the nanoparticles were assessed against pathogenic bacteria Shigella dysenteriae, Klebsiella pneumoniae, Acinetobacter baumannii, Streptococcus pyogenes, and pathogenic fungi and molds Candida albicans, Fusarium oxysporum and Aspergillus fumigatus. The magnetite nanoparticles were moderately effective against all tested pathogens, but the activity of the cobalt-doped nanoparticles was significantly lower, possibly due to an interruption of the Fenton reaction at the bacterial membrane. This work suggests that potentially doping magnetite with stronger metal oxidants may instead enhance their antimicrobial effects

The synthesis of methotrexate-loaded F127 microemulsions and their in vivo toxicity in a rat model

Methotrexate (MTX) has been often formulated as nano and micro-emulsions, nominally to address its poor solubility and off-target effects. Nanoformulated MTX is universally reported to be a more efficacious anti-cancer agent than direct-dissolved drug; however, these investigations generally fail to screen for in vivo toxicity. This study aims to remedy this oversight. MTX was formulated as a standard Pluronic oil-in-water microemulsion with good drug encapsulation efficiency (73.0% ± 8.4). Preliminary in vitro free radical scavenging studies found that formulation reduces drug oxidation four-fold. The toxic effects of formulated and unformulated MTX were investigated in a Wistar rat model. Rats received 0.05 mg/kg MTX as either the microemulsion or directly dissolved in phosphate-buffered saline. A drug-free microemulsion, PBS solution, and saline solution were used as controls. After 28 days, serum levels of enzymes indicative of kidney and liver damage were quantified. Significantly higher serum liver, and serum kidney enzymes were observed in the rats that received the directly dissolved MTX drug (P \u3c 0.05) compared to those who received the encapsulated form. Following sacrifice, the levels of catalase and superoxide dismutase (SOD) were significantly lower and the level of malondialdehyde higher, in rats who received either form of MTX relative to untreated controls. However, the SOD levels were lower in those who received the microemulsion than those who received free MTX. Histology supported the observation that the microemulsion formulation caused no gross structural toxicity to the liver, unlike the free drug. Although toxicity was reduced compared to the free drug, the microemulsion still caused damage to the kidneys. This organ-specific toxicity is consistent with the mode of clearance of the drug. This data demonstrates that the toxicity of formulated drugs must be considered when discussing the relative merits of formulations: encapsulation almost always improves efficacy but may not improve safety

Study of Toxic Effects of Oxothiazole Derivative as a New Antibacterial Agent

The spread of antibiotic-resistant bacteria in many humans and animals has driven researches to identify and design novel antibacterial agents. In vitro inhibitory activity of (2E)-2-(4,5-dihydro-4-oxothiazol-2-yl)-2-(thiazolidin-2-ylidene) acetonitrile against many bacterial pathogens has been proven in both veterinary and human medicine. In this study, its in vivo toxic effects was studied in mice. The median lethal dose (LD50) value of 239.88 mg/kg was estimated using intraperitoneal injection in 8 groups of mice after 48 h treatment. Then, intraperitoneal injections of LD50 of oxothiazole solution into 4 other mice were done to evaluate histopathological changes in their liver and kidney tissues. The histopathological studies were identified as fatty change, hepatitis, necrosis and regeneration in liver, and fibrosis, necrosis, nephritis, hyaline cast and hyperaemia in kidney. In conclusion, the synthesized oxothiazole derivative causes renal and hepatic toxicity in mice at medium concentrations. The change of thiazole substituents and complexation may reduce its toxicity

Erratum to: A Comparative Study on the Antibacterial Effects of Some Newly Synthesized Thiazole, Imidazolidine and Tetrahydropyrimidine Derivatives Against Bacillus cereus and Salmonella typhimurium

Background: Bacillus cereus and Salmonella typhimurium are important human pathogenic bacteria. The spread of strains of drug-resistant these pathogens has encouraged researchers to identify and use novel antibacterial compounds. In this research project, we studied antibacterial effects of some newly synthesized thiazole, imidazolidine and tetrahydropyrimidine derivatives against B. cereus and S. typhimurium. Methods: 2-(E)-Cyano(thiazolidin-2-ylidene)thiazoles 1-4 and (imidazolidin or tetrahydropyrimidin-2-ylidene)malononitriles 5-11 were synthesized. Then, the disk diffusion and broth microdilution methods were applied to evaluate antibacterial effects. Results were recorded as the minimum inhibitory concentrations (MICs) and the growth inhibition zone diameters. Results: The in vitro assessment of antibacterial effects showed that only thiazole derivative 4 had considerable inhibitory effects against B. cereus and S. Typhimurium, whereas the others didn't have so. The inhibitory effects of thiazole derivative 4 against B. cereus and S. typhimurium were proven according to the MICs 125 and 500 µg/mL and the growth inhibition zone diameters 19.2±0.1 and 8.4±0.2 mm, respectively. Conclusion: The antibacterial effects of thiazole, imidazolidine and tetrahydropyrimidine derivatives were different, these effects were observed only in thiazole derivative 4. It could be due to the presence of 4-thiazolone ring in derivative 4, witch could reinforce these effects. After confirming that compound 4 is bactericidal against B. cereus and S. typhimurium, further studies can be accomplished on the determination of the cytotoxic and therapeutic effects of this compound in laboratory animals

Antibacterial effects of novel thiazole derivatives and the toxicity of oxothiazole on liver histopathology of mice

Abstract Background and Objectives: Antibiotic resistance in bacteria has actuated researchers toward evaluating many new antibacterial compounds of which are the thiazoles. In this research the inhibitory effects of novel thiazole derivatives were unraveled on Staphylococcus aureus, Streptococcus agalactiae, Pseudomonas aeruginosa and Klebsiella pneumoniae and oxothiazole liver toxicity effects were assessed on mice. Methods: The antibacterial effect of thiazole derivatives was evaluated by measuring the halo zone with disk diffusion method and dilution procedure in microplate in order to discriminate the minimum inhibitory concentration (MIC) and the liver toxicity of oxothiazole, also, was discerned by injecting 160 mg/kg, 265 mg/ kg and 350 mg/kg doses to mice as well as scrutinizing the liver histopathology. Results: Derivatives utilized in experiment had no inhibitory effect on Pseudomonas aeruginosa and Klebsiella pneumoniae, though their inhibitory effect was observed on Staphylococcus aureus and Streptococcus agalactiae. For Staphylococcus aureus and Streptococcus agalactiae the diameters of growth inhibition zone were 8.9-22.3 mm and 16.1-25.6 mm, respectively and MIC of 50-200 and 25-100 µg/ml by order. Additionally, by increasing the injection dose of oxothiazole with 160 mg/ml, 265 mg/ml and 350 mg/ml doses, the hepatitis lesions and liver necrosis were observed in experimental mice. Discussion: The thiazole derivatives possessed more inhibitory trace on gram positive bacteria than gram negative ones. Furthermore, the likely presence of oxygen link to thiazole ring in tested compounds results in the enhancement of inhibitory potency of these substances. Besides, our results suggest that high doses of oxothiazole cause severe liver damage and rapid death less than 24 hours

Determination of Chemical Composition, and Antiradical and Antimicrobial Capacities of Hydroalcoholic Extracts of Ficus johannis Boiss.

Introduction: Ficus johannis Boiss. is a shrubby species in the family Moracae, exclusively found in Iran, Afghanistan, and Pakistan. This research studies the total phenolic content, flavonoid concentrations, antioxidant capacity, and antimicrobial activity of this biologically unknown species. Materials and Methods: The plant materials were gathered from the northern slope of Taftan Mountain in Sistan and Baluchestan, in the summer of 2022. After washing, drying, grinding, and obtaining hydroalcoholic extracts of the fruits and leaves, the quantification of the phenolic and flavonoid concentrations was done spectrophotometrically utilizing the Folin-Ciocalteu and aluminum chloride colorimetric techniques. The anti-radical activity of the organs was assayed via the DPPH protocol and their antimicrobial effects were assessed using the broth microdilution and streak plate techniques against six bacterial, and three fungal pathogens. Results: The phenolic compounds were found to be evenly distributed in both leaf and fruit extracts (around 1000 µg GAE/g dry extract) while flavonoids were detected in significantly higher concentrations in the fruit extract (541.17 vs 427.24 µg QrE/g dry extract). The leaf extract was better at scavenging free radicals compared to the fruit extract (IC50 93.79 vs 239.62 μg/ml, respectively), while, both extracts showed higher IC50 values than the positive control. The leaf extract showed better inhibitory effects on the tested microorganisms compared to the fruit extract. The leaf extract was effective against all tested bacteria, whereas, among the investigated fungi, only Aspergillus fumigatus was vulnerable to it. Conversely, the fruit extract was able to prevent the growth of all investigated fungal strains, but only two bacterial strains (Streptococcus pyogenes and Klebsiella pneumonia) were affected by it. Conclusion: The Ficus johannis fruits and leaves are great sources of phenolic and flavonoid compounds with moderate anti-radical capacity. Moreover, the fruit extract mainly contains antifungal ingredients while the leaf extract chiefly includes antibacterial agents

Study of Antibacterial Effect of Novel Thiazole, Imidazole and Tetrahydropyridine Derivatives against Escherichia coli

&gt; Introduction: Escherichia coli is one of the important pathogens in human with globalimportance. Because of the necessity for identification and the use of novel antibacterialcompounds against E. coli, in this present study we focused on the antibacterial effects ofsynthesized thiazole, imidazole and tetrahydropyridine derivatives on E. coli.Methods: For evaluation of antibacterial effect, the disk diffusion method was applied to measurethe growth inhibition zone diameter and broth micro-dilution was performed to determine theminimum inhibitory concentration (MIC).Results: Assessing the antibacterial effect showed that only 6d derivative of thiazole hadinhibitory effect on E. coli and the other thiazole, imidazole and tetrahydropyridine derivativeslacked any inhibitory result on this organism. The inhibitory effect of 6d derivative of thiazolewas MIC=125 and growth inhibition zone diameter of 16±0.1.Discussion: The antibacterial effect of thiazole, imidazole and tetrahydropyridine derivativesdiffers from each other and chemical linkages such as oxygen to thiazole ring in 6d derivative,could have reinforced this effect. The next step is determination of the toxicity and therapeuticeffects in the laboratory animals.</span