<span style="font-size:21.5pt;mso-bidi-font-size:14.5pt">Chemistry of pyrones: Part I-Synthesis of triketones and triketoesters and related 4<i style="mso-bidi-font-style: normal">H</i>-pyran-4-ones^† <span style="font-size:18.0pt; mso-bidi-font-size:11.0pt;font-family:Arial"> </span></span>

190-197<span style="font-size:15.5pt;mso-bidi-font-size:8.5pt; font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" mso-ansi-language:en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">Variety of triketones 3a-d and triketoesters 3e-g have been synthesized, characterized and cyclized to the corresponding 4<i style="mso-bidi-font-style: normal">H-pyrones 4a-g.The pyronecarboxylates 4e-g have been converted to the corresponding pyronecarboxamides <b style="mso-bidi-font-weight: normal">5e-g. Dehydration of these carboxamides produces the cyanopyrones 6e-g. Finally cyanopyrones are converted to the tetrazolylpyrones 7e,f<span style="font-size:18.0pt; mso-bidi-font-size:11.0pt;font-family:" times="" new="" roman";mso-fareast-font-family:="" "times="" roman";mso-ansi-language:en-us;mso-fareast-language:en-us;="" mso-bidi-language:ar-sa"="">.</span

Expression, Purification and Characterization of Functional Teduglutide Using GST Fusion System in Prokaryotic Cells

Purpose: Teduglutide is the first and only FDA-approved drug for long-term treatment of short bowel syndrome (SBS). The current study aimed to present an approach for production of teduglutide using recombinant DNA technology. Methods: The coding gene for teduglutide was cloned into pGEX-2T vector, where coding sequence for factor Xa cleavage site was added between GST and teduglutide coding genes. The GST-teduglutide protein was overexpressed in E. coli BL21 (DE3) strain and affinity purified using glutathione sepharose affinity column. Results: On-column proteolytic activity of factor Xa followed by size exclusion chromatography resulted in the pure teduglutide. Circular dichroism (CD) spectropolarimetry showed that the produced teduglutide folds into mainly α-helical structure (>50%), as expected. In mass spectroscopy analysis, the fragments of teduglutide resulted by cyanogen bromide cleavage as well as those expected theoretically due to mass fragmentation were identified. The functionality of the produced peptide was evaluated by measuring its proliferative effect on Caco2 intestinal epithelial cells, and the results indicated that produced teduglutide induces cell proliferation by 19±0.30 and 33±7.82 % at 1.21 and 3.64 µM concentrations, respectively, compared to untreated cells. Conclusion: Teduglutide was successfully expressed and purified and its functionality and structural integrity were confirmed by in vitro experiments. We believe that the experimental-scale method presented in the current study can be useful for pilot-scale and also industrial-scale production of teduglutide

Solubility of mesalazine in pseudo-binary mixtures of choline chloride/ethylene glycol deep eutectic solvent and water at 293.15 K to 313.15 K

Abstract Mesalazine (5-ASA) is a medication utilized to treat inflammatory bowel diseases involving ulcerative colitis and Crohn’s disease. Mesalazine has fewer side effects but the low solubility and bioavailability of it is responsible for its delayed onset of action. Hence, the goal of this study is to determine the molar solubility of 5-ASA in aqueous pseudo-binary mixtures containing low toxic biocompatible choline chloride/ethylene glycol deep eutectic solvent (ChCl/EG DES) with DES mass fraction of 0.0–1.0 using a shake-flask technique at 293.2–313.2 K and approximately 85 kPa. The experimental results indicated that the solubility of 5-ASA enhanced by addition of DES mass fraction and also increasing temperature. The molarity values of 5-ASA were then modelled by some traditional cosolvency models, and regressed each model parameters. The back-computed molarity of 5-ASA using the selected cosolvency models presented a good consistency with the experimental data (lower mean percentage deviation than 5.14%). Moreover, the Gibbs and van’t Hoff equations were employed to compute the thermodynamic functions of 5-ASA dissolution process in ChCl/EG DES + water from the temperature dependency of solubility data. This analysis presented an endothermic and entropy-driven process of 5-ASA dissolution in ChCl/EG DES + water. Furthermore, enthalpy-entropy compensation analysis represented non-linear enthalpy dissolution vs. Gibbs free energy compensation plots with positive and negative slopes for 5-ASA whereas the positive and negative slopes were probably due to the enhance in solvation of 5-ASA by ChCl/EG DES molecules and the solvent-structure loosing, respectively

An update on actively targeted liposomes in advanced drug delivery to glioma

High-grade glioma is one of the most aggressive types of cancer with a low survival rate ranging from 12 to 15 months after the first diagnosis. Though being the most common strategy for glioma therapy, conventional chemotherapy suffers providing the therapeutic dosage of common therapeutics mostly because of limited permeability of blood-brain barrier (BBB), and blood-brain tumor barrier (BBTB) to anticancer agents. Among various nanoformulations, liposomes are considered as the most popular carriers aimed for glioma therapy. However, non-targeted liposomes which passively accumulate in most of the cancer tissues mainly through the enhanced permeation and retention effect (EPR), may not be applicable for glioma therapy due to BBB tight junctions. In the recent decade, the surface modification of liposomes with different active targeting ligands has shown promising results by getting different chemotherapeutics across the BBB and BBTB and leading them into the glioma cells. The present review discusses the major barriers for drug delivery systems to glioma, elaborates the existing mechanisms for liposomes to traverse across the BBB, and explores the main strategies for incorporation of targeting ligands onto the liposomes. It subsequently investigates the most recent and relevant studies of actively targeted liposomes modified with antibodies, aptamers, monosaccharides, polysaccharides, proteins, and peptides applied for effective glioma therapy, and highlights the common challenges facing this area. Finally, the actively targeted liposomes undergoing preclinical and clinical studies for delivery of different anticancer agents to glioma cells will be reviewed