Synthesis, spectral characterization, anti-bacterial, cytotoxic evaluation and docking studies of new urea and thiourea derivatives

Isoniazid is one of the main API’s used in the combination treatment of tuberculosis recommended by the WHO. Urea and its derivatives are an important class of heterocyclic compounds that possess a wide range of therapeutic and pharmacological properties, while thiourea is an organosulphur compound in that it resembles urea except that the atom oxygen has been replaced by a Sulphur atom, but the properties of urea and thiourea are significantly different. The current work concerns the synthesis of a new class of urea and thiourea derivatives of isoniazid with various isocyanates and isothiocyanates in the presence of trimethylamine. The IR and NMR spectral data were performed for the urea and thiourea derivatives of the compounds [(3c & 3f) & (3d & 3e)], respectively. Molecular docking studies of the compounds (3a-h) revealed the binding mode involved in the active site of DNA gyrase. The synthesized urea and thiourea derivatives of isoniazid with various isocyanates and isothiocyanates were tested for their antibacterial activity against gram-positive and gram-negative bacteria using the “disc diffusion method”. Of all compounds tested, the urea derivatives (3a &3d), the thiourea derivatives (3e & 3g) showed more potent activity than the other compounds. The MTT assay revealed concentration dependent cytotoxic effects over a concentration range 25-200 µg/mL.

Optimization of Biostimulants Application for Phenology and Quality of Oats

Abstract In modern agriculture the use of biostimulants not only reduces the cost of production but also increase yield and quality of crops without harming environment. The response of fodder oat to biostimulants was evaluated in a pot experiment using four biostimulants at different concentrations i.e Moringa leaf extract at ratio of 1:10, 1:20, 1:30, 1:40, 1:50, Sea weed extract at 1%, 2%, 3%, 4%, 5%, Thiourea at 100 ppm, 200 ppm, 300 ppm, 400 ppm, 500 ppm and Chitosan at 25 ppm, 50 ppm, 100 ppm, 125 ppm, 150 ppm. Oat crop was treated with biostimulants using foliar application, at two growth stages i.e tillering and booting. Data on various agronomic and quality parameters were recorded and analyzed. Results showed that biostimulants significantly affected phenology and quality of oat. The highest green fodder yield (872.32 g) was observed in the pots treated with 2%Solution of seaweed extract similarly highest dry matter yield was also highest at 170.85 g Interestingly crude protein was highest for thiourea at 400 ppm. In each biostimulant following doses stood out both in terms of yield and quality. In case of moringa leaf extract the ratio of 1:40with 900 g per pot yield and 9.43 % protein, for sea weed extract 2% was better than other doses with 981 g yield and 9.17% protein, for thiourea the 400 ppm was better than other concentrations as it shows highest yield (872.32 g) and crude protein (9.52%) and for chitosan 100 ppm was comparatively better in performance with 964.98 g yield per pot and 9.35% CP. It is concluded from our study that biostimulants improve fodder oat yield and quality.

Effect of Thiourea on Physiological Performance of Two Salt Affected Rice (Oryza sativa L.) Cultivars

Aims: The aim of the experiment was to investigate the effect of thiourea on physiological characteristics of two rice (Oryza sativa L.) varieties under impact of salinity. Study Design: Experiment includes two rice varieties named as B-515 and KS-282, salinity level of 150 mM, thiourea of 0.25 mM alone and in combination were arranged in a completely randomized design (CRD). Place and Duration of Study: Old Botanical Garden, University of Agriculture Faisalabad, Pakistan, between 4th July and 21st August 2015. Methodology: Transplants of two rice varieties, Basmati-515 and KS-282 were exposed to salinity (150 mM) and thiourea (0.25 mM) after one month of transplanting in a Completely Randomized Design with three replications. Harvesting data was taken that include fresh and dry weights, leaf area, number of tillers, photosynthetic pigments, photosynthetic rate, transpiration rate, stomatal and substomatal conductance, water use efficiency and intrinsic CO2 concentration as well as chlorophyll contents in two rice varieties. Results: Thiourea treatment enhanced photosynthetic efficiency of Basmati-515 more than KS-282 by improving the chlorophyll and carotenoid contents and gas exchange attributes more than control. Conclusion: Salinity profoundly affect the physiological performance of two rice varieties especially that of KS-282, while 0.25 mM thiourea application unable to mitigate the effect of salinity but thiourea alone proved to be beneficial for both the rice varieties.

Technology adaptability research on removal of heavy metals in Acanthopanax senticosus extract with alkyl thiourea functionalised silica / 中草药

Objective: To study on the scavenging rules and optimum processing condition of heavy metals Pb, Cd, Hg, and Cu removal in Acanthopanax senticosus extract (ASE) with alkyl thiourea functionalized silica (ATFS). Methods: ASE was simulated as study object of excessive harmful elements Pb, Cd, Hg, and Cu.The scavenging mass, scavenging time, shaking speed and scavenging temperature were investigated by static scavenging way and the diameter ratio, sample solution, washing speed and washing temperature were investigated by dynamic scavenging way influence to metal removal rate. The best process of static and dynamic was chosen by orthogonal experiment; Eleutheroside B and eleutheroside E were as the effective constituents in ASE, solid contents and HPLC fingerprint similarity were as investigated index, the change of chemical composition in ASE to heavy metals removal from aqueous solution before and after treatment was evaluated. Results: Compared with unmodified silica gel (SG), static absorption and dynamic absorption had a high removal rate of heavy metals, the scavenging speed was relative fast, the best static scavenging process of harmful elements in ASE were: The ratio of TCME mass and adsorbent was 80∶1, shaking speed was 260 times/min, scavenging time was 600 min, scavenging temperature was 45 ℃; The best dynamic scavenging process: Diameter ratio was 1∶20, sample volume was 100 mL, washing speed was 3 BV/h, washing temperature was 15 ℃; The change rate of eleutheroside B and eleutheroside E before and after heavy metal elements in ASE dislodged were less than 2.00%, loss ratio of solid contents was 0.18%, fingerprint similarity was more than 99.9%. Conclusion: The method can be used to satisfy the high efficiency of selective removal of harmful elements in ASE and the effective composition of almost no effect, the method is simple and easy, so it can be recommended for pretreatment of harmful elements in traditional Chinese medicine extracts and this way provides a new thought and research technique to decrease the contents of harmful elements.

Exploring the Synthesis of New 1-(4-Substitutedphenylamino) imidazo[1,5-a]indol-3-one Derivatives as Cyclized Analogs of Leucettines.

New 1-arylaminoimidazo[1,5-a]indol-3-ones were synthesized as cyclized derivatives of leucettine L41, a low molecular weight inhibitor of the DYRKs/CLKs protein kinases with potential applications in Alzheimer's disease and Down syndrome. In this first approach, access to the desired 1-aminoimidazo[1,5-a]indol-3-ones involved 5 steps and was explored with a series of various primary amines and polar secondary amines in order to introduce molecular diversity on N-1 position. The 5 step synthesis of the 1-arylaminoimidazo[1,5-a]indol-3-ones was achieved and the limiting step of this process was the final cyclization via a sulphur/nitrogen displacement from methylsulfanyl thiourea intermediates. Good results were obtained for isothioureas derived from primary amines. The 1-arylaminoimidazo[1,5-a]indol-3-ones were evaluated on a panel of five protein kinases (DYRK1A, CK1, CDK5/p25, GSK3 and CLK1).

Amperometric Immunosensor Based on Layer-by-layer Assembly of Thiourea and Nano-gold Particles on Gold Electrode for Determination of Naphthalene / 分析化学

A new type of amperometric immunosensor for the determination of naphthalene based on self-assemble) layer-by-layer technique was reported. The preparation procedure of such a sensor was characterized and the operation conditions, such as the pH value of supporting solution, incubated temperature and time were studied by cyclic voltammetry. Under the optimized working conditions, the current response of the immunosensor) was proportional to the concentration of naphthalene in the range of 0.5-100 μg/L with a detection) limit of 0.08 μg/L(r=0.9986). This method was applied to the naphthalene detection in river) water) samples and the recovery was ranging in 94.3%-107.0%. The reported immunosensor exhibited high sensitivity and long-term stability for naphthalene detection, and was easy to be prepared and regenerated.

Pathologic Changes of Ganglion Cell and Nerve Plexus in Internal Anus Sphincter of Rats with Congenital Anorectal Malformations / 中国康复理论与实践

@#Objective To observe the pathologic changes of ganglion cell and nerve plexus in internal anus sphincter of rats with congenital anorectal malformations (ARM).Methods Healthy and pregnant Wistar-Imammichi rats were induced to ARM by ethylene thiourea (ETU). There were 67 rats with ARM at all. The pelvis was continuously cut from the exactly midsagittal plane. The HE staining was performed, and the numbers of the ganglion cell and nerve plexus in the internal anus sphincter were observed under the microscope.Results The average numbers of the ganglion cell and nerve pluxes in the ARM embryos were (1.206±0.012) and (0.308±0.051). Those of the normal control embryos were (3.710±0.043) and (1.227±0.072) respectively. There was a significant difference between two groups ( P<0.05～0.01). While, those of the embryos without ARM which dealt with ETU were (3.012±0.032) and (1.187±0.004) respectively, didn't differ from the normal control embryos.Conclusion The decrease of the ganglion cell and the nerve plexus in internal anus sphincter is an important pathologic change of ARM.

Determination of Mercury in Blood by Atomic Fluorescence Spectrometry with a Thiourea Extraction Method / 环境与健康杂志

Objective To develop a method for determination of mercury in blood by atomic fluorescence spectrometry. Methods Using a thiourea extraction method, the mercury in blood is determined by atomic fluorescence spectrometry. Results The linearity of calibration curve of mercury was in the concentration of 0.000-10.00 ?g/L. The detection limit was 0.06 ?g/L. The recovery rates were 95.5%-100.3%.The RSDs were 4.1%-4.5%. Conclusion The method has the advantages of simple operation, high sensitivity, good repeatability and is applicable to the determination of mercury in blood.

Determination of Total Selenium in Salt by Hydride Generation-Atomic Fluorescence Spectrometry / 环境与健康杂志

Objective To establish a sensitive, reliable and simple method for determination of selenium(Se) in salt. Methods The salt samples were dissolved in water and added hydrochloric acid, thiourea, placed for 30 minutes under the room temperature, then used HG-AFS to determine Se. Results The linear range was 0.5-20 ?g/L, the detection limit was 0.06 ?g/L, RSD

Gene Expression of Surfactant Protein B and C in Endotoxin and Thiourea Treated Rats / 결핵

BACKGROUND: The surfactant specific proteins, SP-B and SP-C are believed to be important regulators of the surfactant function and homeostasis. Since acute respiratory distress syndrome(ARDS) is usually viewed as the functional and morphological expression of a similar underlying lung injury caused by a variety of insults, and since abnormalities in the surfactant function have been described in ARDS, the authors investigated the different effects of endotoxin and thiourea on the accumulation of mRNA encoding SP-B and SP-C. METHODS: Sprague-Dawley rats were given 5 mg/kg of an intraperitoneal endotoxin from Salmonella enteritidis and 3.5 mg/kg intraperitoneal thiourea and were sacrificed at different time periods. RESULTS: 1. The SP-B mRNA levels 6 and 24 hours after the 5 mg/kg endotoxin treatment was significantly reduced by 26.1% and 50%, respectively(P<0.01, P<0.001). 2. The SP-B mRNA levels 24 hours after the 3.5 mg/kg thiourea treatment was reduced by 9.8% and 12.5%, respectively. 3. The SP-C mRNA levels 6 and 24 hours after the 5 mg/kg endotoxin treatment was significantly reduced by 38.7% and 53.6%, respectively(P<0.01, P<0.001). 4. The SP-C mRNA level 6 hours after the 3.5 mg/kg thiourea treatment was reduced by 22.8%(P<0.05). CONCLUSION: These results indicate that the differential regulation of the hydrophobic surfactant proteins in vivo is evident, and suggest that the hydrophobic surfactant proteins might be differentially regulated during lung injury at different time periods without altering the lung wet to dry ratios. The mechanism of these alternations at the different time periods and the different kinds of etiology remain to be determined.

Gene Expression of Surfactant Protein A mRNA of the Lung in Endotoxin and Thiourea Treated Rats / 결핵

BACKGROUND: The surfactant protein A(SP-A) is important in the regulation of surfactant secretion, synthesis and recycling. Since the acute respiratory distress syndrome(ARDS) is usually viewed as the functional and morphological expression of a similar underlying lung injury caused by a variety of insults and since abnormalities in surfactant function have been described in ARDS, the authors investigated the different effects of endotoxin and thiourea on the accumulation of mRNA encoding SP-A. METHODS: Sprague-Dawley rats were given 5 mg/kg intraperitoneal endotoxin from Salmonella enteritidis and 3.5 mg/kg intraperitoneal thiourea and sacrified at different time periods. RESULTS: 1) SP-A mRNA was significantly increased 67.0% in 6 hours and 73.4% in 24 hours after 5 mg/kg endotoxin treatment respectively(P<0.005, P<0.005). 2)SP-A mRNA was significantly decreased 32.9% in 24 hours after 3.5 mg/kg thiourea treatment(P<0.05). CONCLUSIONS: These results indicate that the differential regulation of surfactant protein A in vivo is evident and suggest that surfactant protein A might be differentially regulated during different kind of insults of lung injury at different time periods without altering lung wet to dry ratios.