Combinatorial Chemistry & High Throughput Screening - Volume 21, Issue 7, 2018

Aim and Objective: Ultrafine Ag/ZnO nanotetrapods (AZNTP) have been prepared successfully using silver (I)–bis (oxalato) zinc complex and 1, 3-diaminopropane (DAP) with a phase separation system, and have been injected into a diethyl/water solution. Materials and Methods: This crystal structure and lattice constant of the AZNTP obtained were investigated by means of a SEM, XRD, TEM and UV-vis spectrum. Results: The results of the present study demonstrated the growth and characterization AZNTP for humidity sensing and DAP plays a key role in the determination of particle morphology. AZNTP films with 23 nm in arm diameter have shown highly sensitive, quick response sensor material that works at room temperature.

Background: A set of antibiotic fluoroquinolones with confirmed antimicrobial activity were analyzed with the use of two types of quantum chemical calculation methods and quantitative structure-activity relationships (QSAR). Objective: The purpose of this study was to demonstrate the common and differentiating characteristics of the above-mentioned chemical compounds alike physicochemically as well as pharmacologically based on the quantum chemical calculations and microbiological activity data. Methods: During the study PCA and MLR analysis were performed, as the types of proposed chemometric approach. The semi-empirical level of in silico molecular modeling was performed for calculations of molecular descriptors. Results: QSAR models were proposed based on chosen descriptors. The relationship between the structure and microbiological activity and physicochemical parameters data was able to class and describe them with the use of statistically significant molecular descriptors. Conclusion: The applied chemometric approaches revealed the influential features of tested structures responsible for the antimicrobial activity of analyzed compounds.

Background: In recent times, computer aided methodologies have received broad attention in drug development. These studies have improved the accuracy and shortened the time frame to identify suitable drug candidates from large datasets. Xanthine is a plant alkaloid which also acts as an intermediate product on the pathway of purine degradation. Xanthine acts as scaffold for various natural and synthetically derived bioactive molecules. Objective: The present work aims to screen xanthine derivatives targeting phosphodiesterase 9A (PDE9A), one of the most important regulatory protein of signal transduction. Method: In silico approach such as Virtual screening, molecular docking and molecular dynamic was attempted to screen a repertoire of 2055 xanthine derivatives extracted from ZINC database against PDE9A. The potency of the resultant screened compound was finally validated by spectrophotometric malachite green inhibition assay. Results: Preliminary virtual screening narrowed down the compounds to a list of 10 which is followed by a second round of stringent screening using molecular docking approach. Top four hits were selected for thorough interaction analysis with PDE9A. The molecular docking analysis of best ranked compound, ZINC62579975 (-12.59) revealed its potential to establish essential chemical interactions with inhibition determining key residues in the PDE9A active site. The stability of ZINC62579975 in PDE9A was further validated by 6 ns molecular dynamic simulation studies. The in vitro malachite spectrophotometric assay confirmed the bioactive potential of the above compound. Comparative inhibition studies asserted more potency of ZINC62579975 towards PDE9A (46.96 ± 1.78 μM) than PDE5A (61.023 ± 1.71 μM) and PDE4D (70.04 ± 1.98 μM). Conclusion: The entire study validates ZINC62579975 as a potent candidate molecule for PDE9A inhibition. The present study provides a roadmap for future drug designing of more potent xanthine derivatives. This study also explores the potential of xanthine scaffold in future drug development process.

Aim and Objective: One of the principles of green chemistry is using inexpensive reagents and catalysts to design green route for synthesis of organic compounds. Recently magnetic nanoparticles have provided a considerable merits. In this study, hollow Fe3O4@Dopamine-SO3H has been successfully applied for the green synthesis of tetrahydrobenzo[b]pyrans and spirooxindoles via one-pot multi-component reaction. Materials and Methods: Chemical reagents were purchased from Merck and Aldrich. Melting points were determined using an Electrothermal 9100. Fourier transform infrared and NMR spectra were recorded with a Shimadzu 8400 spectrometer and Bruker spectrometer, respectively. Results: The reaction between benzaldehyde, malononitrile and dimedone was selected as the model for synthesis of tetrahydrobenzo[b]pyran. The obtained results showed that the best amount of catalyst is 0.01 g and the reaction has occurred in solvent free condition at 70°C. The results showed that both electron-withdrawing and electron-donating substituents have an acceptable yield in the reaction. After that the scope of this method was evaluated in one-pot synthesis of spirooxindole derivatives through three-component reaction of isatin derivatives, malononitrile or ethyl cyanoacetate and 1,3-cycllic diketone. The optimum condition was 0.01 g catalyst using H2O under reflux condition. Then other derivatives produced in excellent yields during short reaction times. Conclusion: Tetrahydrobenzo[b]pyran and spirooxindole derivatives in the presence of this catalyst were synthesized. The ease of preparation and handling of the catalyst and operational simplicity are some of the main advantages of this work. In addition, the catalyst could be recycled and reused at least six times without notable reduction in its catalytic activity.

Aim and Objective: Formation of the gallbladder stones is a common disease and a major health problem. The present study aimed to identify the structures of the most common types of gallbladder stones using X-ray spectroscopic techniques, which provide information about the process of stone formation. Material and Method: Phase and elemental compositions of pure cholesterol and mixed gallstones removed from gallbladders of patients were studied using energy-dispersive X-ray spectroscopy combined with scanning electron microscopy analysis and X-ray diffraction. Results: The crystal structures of gallstones which coincide with standard patterns were confirmed by X-ray diffraction. Plate-like cholesterol crystals with laminar shaped and thin layered structures were clearly observed for gallstone of pure cholesterol by scanning electron microscopy; it also revealed different morphologies from mixed cholesterol stones. Elemental analysis of pure cholesterol and mixed gallstones using energy-dispersive X-ray spectroscopy confirmed the different formation processes of the different types of gallstones. Conclusion: The method of fast and reliable X-ray spectroscopic techniques has numerous advantages over the traditional chemical analysis and other analytical techniques. The results also revealed that the X-ray spectroscopy technique is a promising technique that can aid in understanding the pathogenesis of gallstone disease.

Aim and Objective: Plant diseases are caused by fungal pathogens lead to severe economic losses in many agriculture crops. And the increasing resistance of many fungi to commonly used antifungal agents necessitates the discovery and development of new fungicides. So this study was focused on synthesizing novel skeleton compounds to effectively control plant diseases. Materials and Methods: A series of drimane-amide derivatives were designed, synthesized by aminolysis reaction of amine with intermediate sclareolide which was prepared from sclareol. The structures of all the synthesized compounds were confirmed using 1H NMR, 13C NMR, and HRMS (ESI) spectroscopic data. Their in vitro antifungal activity were preliminarily evaluated by using the mycelium growth rate method against five phytopathogenic fungi: Botrytis cinerea, Glomerella cingulata, Alternaria alternate, Alternaria brassicae, and Fusarium graminearum. Results: 23 target compounds were successfully obtained in yields of 52-95%. Compounds A2 and A3 displayed favorable inhibitory potency against B. cinerea, G. cingulata and A. brassicae with IC50 values ranging from 3.18 to 10.48 μg/mL. These two compounds displayed higher fungicidal activity than sclareol against all the tested phytopathogenic fungi, and were more effective than the positive control thiabendazole against A. alternate and A. brassicae. The structure-activity relationship studies of compounds A1-10 indicated that both the position and type of substituent on the phenyl ring had significant effects on antifungal activity. Conclusion: The drimane-amide derivatives A2 and A3 were the most promising derivatives and should be selected as new templates for the potential antifungal agents.

Background: Neonatal sepsis is considered as the most frequent cause of death in newborns. Early diagnosis is important to reduce mortality and morbidity. The rapid progression of the disease requires proper use of biomarkers specific for prompt diagnosis and intervention. Objective: We aimed to evaluate the benefit of interleukin-33 serum levels in the diagnosis and treatment of neonatal sepsis. Method: We included 51 infants with neonatal sepsis as the main study group and 50 neonates without sepsis as the control group. Serum levels of interleukin-6, interleukin-33 and C-reactive protein were measured on the 1st, 3rd and 7th days of sepsis in the study group and on the 3rd postpartum day in the control group, respectively. Results: Serum levels of interleukin-6, interleukin-33 and C-reactive protein were significantly higher in the first day of sepsis. Serum levels of interleukin-6, interleukin-33 and C-reactive protein decreased significantly on the 3rd and the 7th days of antibiotic treatment. We found a significant relationship between interleukin-33 and C-reactive protein and between interleukin-6 and C-reactive protein on the first day of sepsis. Conclusion: Serum interleukin-33 level is up-regulated in neonatal sepsis, which might be used as a novel diagnostic marker and also a useful tool to predict prognosis in early neonatal sepsis.

Aim and Objective: As is known, AA, EP and UA can also coexist in biological fluids. Therefore, the determination of the levels of these compounds in biological fluids is extremely important both for the diagnosis and treatment of the related diseases. In the presence of many interfering substances in biological fluids such as blood and urine samples, it is very important that these compounds can be selectively analyzed. Materials and Methods: All electrochemical experiments were performed using an Autolab PGSTAT 128N potentiostat. Before beginning the electrochemical measurements, the PGE was activated. The electrochemical pretreatment of PG was exercised by anodically +1.40 V for 60 s. Then, measurements were performed with CV (-0.4 V to 1.2 V) and DPV (-0.2 V to 0.7 V) for single and simultaneous voltammetric behaviour of AA, EP, and UA in the electrochemical method. Results: The anodic peak potentials of AA and UA were observed at about +0.32 V and +0.62 V, respectively. On the other hand, for EP, while anodic peak potential was observed at about +0.53 V, in the reverse scan, cathodic peak potentials were observed at about +0.41 V and +0.007 V. The reduction peak observed at +0.3 V with the oxidation peak observed at +0.53 V are the reversible peaks. In the method developed for the electrochemical simultaneous determination of AA, EP and UA using PGE with DPV technique in BR buffer solution (pH 4.0), the anodic peak potentials are sufficiently separated from each other. Conclusion: A voltammetric method was developed for the simultaneous determination of AA, EP and UA with PGE for the first time. Here, the most important thing is that the simultaneous determination of AA, EP and UA was successfully achieved with that targeted voltammetric method which was sensitive, low-cost, practical and well-repeated; and that these were proven to be selectively applicable in pharmaceutical products and biological liquids.

Aim and Objective: In this work, we synthesized and characterized a novel Brönsted acidic ionic liquid from the reaction of N, N, N', N'-tetramethylethylenediamine with chlorosulfonic acid and explored its catalytic activity in 1, 8-dioxo-octahydroxanthenes synthesis. Materials and Methods: Dimedone, aryl aldehydes, and the ionic liquid as the catalyst were reacted under solvent-free conditions. The progressive of the reaction was monitored by a thin layer of chromatography (ethyl acetate/n-hexane = 1/5). All products were characterized as the basis of their spectra data and melting point by comparison with those reported in the literature. Results: The prepared ionic liquid was successfully applied in the synthesis of 1, 8-dioxooctahydroxanthenes in good to high yields on the reaction of aryl aldehyde and dimedone at 120oC under solvent-free conditions. Conclusion: This research demonstrates that the catalyst is impressive for 1, 8-dioxo-octahydroxanthenes synthesis under solvent-free conditions.

Aim and Objective: Quantitative Structure- Property Relationship (QSPR) has been widely developed to derive a correlation between chemical structures of molecules to their known properties. In this study, QSPR models have been developed for modeling and predicting thermodynamic properties of 76 camptothecin derivatives using molecular descriptors. Materials and Methods: Thermodynamic properties of camptothecin such as the thermal energy, entropy and heat capacity were calculated at Hartree–Fock level of theory and 3-21G basis sets by Gaussian 09. Results: The appropriate descriptors for the studied properties are computed and optimized by the genetic algorithms (GA) and multiple linear regressions (MLR) method among the descriptors derived from the Dragon software. Leave-One-Out Cross-Validation (LOOCV) is used to evaluate predictive models by partitioning the total sample into training and test sets. Conclusion: The predictive ability of the models was found to be satisfactory and could be used for predicting thermodynamic properties of camptothecin derivatives.