Design and synthesis of 4,5-diphenyl-imidazol-1,2,3-triazole hybrids as new anti-diabetic agents: in vitro α-glucosidase inhibition, kinetic and docking studies.

Fourteen novel 4,5-diphenyl-imidazol-1,2,3-triazole hybrids 8a-n were synthesized with good yields by performing click reaction between the 4,5-diphenyl-2-(prop-2-yn-1-ylthio)-1H-imidazole and various benzyl azides. The synthesized compounds 8a-n were evaluated against yeast α-glucosidase, and all these compounds exhibited excellent inhibitory activity (IC50 values in the range of 85.6 ± 0.4-231.4 ± 1.0 µM), even much more potent than standard drug acarbose (IC50 = 750.0 µM). Among them, 4,5-diphenyl-imidazol-1,2,3-triazoles possessing 2-chloro and 2-bromo-benzyl moieties (compounds 8g and 8i) demonstrated the most potent inhibitory activities toward α-glucosidase. The kinetic study of the compound 8g revealed that this compound inhibited α-glucosidase in a competitive mode. Furthermore, docking calculations of these compounds were performed to predict the interaction mode of the synthesized compounds in the active site of α-glucosidase. A novel series of 4,5-diphenyl-imidazol-1,2,3-triazole hybrids 8a-n was synthesized with good yields by performing click reaction between the 4,5-diphenyl-2-(prop-2-yn-1-ylthio)-1Himidazole and various benzyl azides. The synthesized compounds 8a-n were evaluated against yeast α-glucosidase and all these compounds exhibited excellent inhibitory activity (IC50 values in the range of 85.6 ± 0.4-231.4 ± 1.0 µM), even much more potent than standard drug acarbose (IC50 = 750.0 µM).

A new series of Schiff base derivatives bearing 1,2,3-triazole: Design, synthesis, molecular docking, and α-glucosidase inhibition.

A series of new Schiff bases bearing 1,2,3-triazole 12a-o was designed, synthesized, and evaluated as α-glucosidase inhibitors. All the synthesized compounds showed promising inhibition against α-glucosidase and were more potent than the standard drug acarbose. The kinetic study on the most potent compound 12n showed that this compound acted as a competitive α-glucosidase inhibitor. The docking study revealed that the synthesized compounds interacted with the important residues in the active site of α-glucosidase.

Synthesis of Silica-coated Iron Oxide Nanoparticles: Preventing Aggregation without Using Additives or Seed Pretreatment.

The Stober process is frequently used to prepare silica-coated iron oxide nanoparticles. This is usually achieved by seeding a reaction mixture consisting of water, ethanol and a catalyst with iron oxide particles and adding a silica precursor. The hydrolysis and condensation of precursor monomers results in the deposition of a silica layer on iron oxide particles. However, this process is accompanied by an increase in the ionic strength of the medium which promotes the rapid aggregation of iron oxide particles. A number of methods have been developed to prevent seed aggregation during the coating process. The majority of these methods include a pretreatment step in which the surface of iron oxide particles is modified in a manner that increases their stability in aqueous solutions. Here we suggest that by decreasing the initial concentration of the catalyst for a short period to minimize nucleation by reducing precursor hydrolysis rate and then gradually increasing the concentration to the optimum level to allow silica formation to proceed normally it may be possible to prevent aggregation without surface modification. The properties of the resulting nanoparticles as analyzed by transmission electron microscopy and magnetometry as well as their efficiency at extracting genomic DNA from different bacterial strains compared to that of a commercial extraction kit are also reported.

Covalent immobilization of coagulation factor VIII on magnetic nanoparticles for aptamer development.

INTRODUCTION: Magnetic nanoparticles (MNPs) are one of the most useful particulate systems in analytical applications such as specific aptamer selection. Proteins are the most noted targets of aptamer selection. Generally, covalently immobilized protein coated MNPs are more stable structures. METHODS: In this study, coagulation factor VIII (FVIII) was immobilized on MNPs. A silica coating provided isocyanate functional groups was considered to interact covalently with reactive groups of the protein, resulting in a stable protein immobilization. The reactions was run in dried toluene. At end, these MNPs were applied for affinity determination of a previously selected FVIII specific aptamers. RESULTS: Immobilization of 1 mg FVIII (~ 3 nmol) on 5 mg particles was achieved with no significant particle aggregation. Using a fluorescence-based method, affinity measurement resulted in a calculated dissociation constant of 120 ± 5.6 nM for the FVIII-specific aptamer to the FVIII-coated MNPs. CONCLUSION: The final product could be a suitable protein-coated solid support for magnetic-based aptamer selection processes.

Screening for Type II L-Asparaginases: Lessons from the Genus Halomonas.

Among the two types of bacterial L-asparaginases, only type II enzymes have been used in the treatment of acute lymphoblastic leukemia owing to their higher affinity for L-asparagine. However, current screening media used for the isolation of L-asparaginase-producing microorganisms do not discriminate between the two types of L-asparaginase. During an optimization study conducted to increase L-asparaginase production by environmental Halomonas isolates, it was noticed that the pattern of L-asparaginase production in response to variations in glucose concentration varied between different isolates suggesting that they differ in their ability to produce type II L-asparaginases, an observation that was confirmed by further experiments. Bioinformatics analysis of available Halomonas whole genome sequences revealed that indeed some species of this genus possess both L-asparaginase types while others possess only type I enzymes. By comparing the growth pattern of these isolates on different media, we propose that by omitting glucose, reducing the concentration of L-asparagine and providing an alternative nitrogen source in L-asparaginase screening media it may be possible to differentiate between type I and type II activities.