Synthesis and In-Vivo Evaluation of Benzoxazole Derivatives as Promising Anti-Psoriatic Drugs for Clinical Use

2-(4-Chlorophenyl)-5-benzoxazoleacetic acid (CBA) and its ester, methyl-2-(4-chloro-phenyl)-5-benzoxazoleacetate (MCBA), were synthesized, and their structures were confirmed by ¹HNMR, IR, and mass spectrophotometry. The anti-psoriatic activities of CBA and MCBA were tested using an imiquimod (IMQ)-induced psoriatic mouse model, in which mice were treated both topically (1% w/w) and orally (125 mg/kg) for 14 days. The erythema intensity, thickness, and desquamation of psoriasis were scored by calculating the psoriasis area severity index (PASI). The study also included the determination of histopathological alterations in the skin tissues of treated mice. Topical and oral administration of CBA and MCBA led to a reduction in erythema intensity, thickness, and desquamation, which was demonstrated by a significant decrease in the PASI value. In addition, skin tissues of mice treated with CBA and MCBA showed less evidence of psoriatic alterations, such as hyperkeratosis, parakeratosis, scale crust, edema, psoriasiform, and hyperplasia. After administration of either topical or oral dosing, the anti-psoriatic effects were found to be stronger in MCBA-treated than in CBA-treated mice. These effects were comparable to those produced by Clobetasol propionate, the reference drug. This drug discovery could be translated into a potential new drug for future clinical use in psoriasis treatment.     

INTERACTION OP POLYVINYL ALCOHOL WITH LECITHIN AT THE AIR/WATER AND OIL/WATER INTERFACES AND ITS EFFECT ON EMULSION STABILITY

The interaction of polyvinyl alcohol (PVA) with lecithin films at the air/water and xylene/water interfaces was studied at pH 3, the isoelectric point of lecithin. Surface and interfacial tension measurements and electro-phoretie mobility data showed that PVA either replaces the lecithin molecules or becomes coadsorbed with it at the interface. This mixed film has no elasticity and very low interfacial viscosity. However, coalescence rate measurements showed that the emulsion formed by the polymer* lecithin is more stable than that formed with either polymer or lecithin alone. The enhanced stability by the PVA-lecithin mixed film was attributed to steric interaction produced by the adsorbed polymer.     

Solubility and Thermal Degradation of Quercetin in CO2-Expanded Liquids

The solubility of quercetin and its thermal degradation was studied in CO₂-expanded ethanol and ethyl lactate. An equipment setup was constructed that enabled the separation of the products of degradation while quantifying the solubility of quercetin. Three different conditions of temperature were analyzed (308, 323, and 343 K) at 10 MPa. Higher solubility and thermal degradation of quercetin were observed for CO₂-expanded ethyl lactate in comparison with CO₂-expanded ethanol. At the same time, as the amount of CO₂ was increased in the CO₂-expanded liquids mixtures, the thermal degradation of quercetin decreased for almost all the conditions of temperature considered in this work. The importance of considering thermal degradation while performing solubility measurements of compounds that are thermally unstable such as quercetin was highlighted.     

Synthesis,cytotoxicity, in-vitro antibacterial screening and in-silico study of novel thieno[2,3-b]pyridines as potential pim-1 inhibitors

Abstract

A novel series of thieno[2,3-b]pyridines was prepared via an one-step protocol in excellent yields. The protocol involved the reaction of pyridine-2(1H)-thiones with the appropriate halogen containing reagents in ethanolic sodium ethoxide solution under stirring at 80?°C for 2?h. The new thienopyridines were screened against different bacterial and fungal strains. Thieno[2,3-b]pyridine-2-carboxylate 9a showed the most effective antibacterial activities against each of Staphylococcus aureus and Escherichia coli with MIC/MBC values of 9.9/19.8 and 19.8/39.5?µM, respectively, when compared with Ciprofloxacin. 9a was the most effective compound against MRSA with inhibition zone of 16.2?±?0.6?mm, when compared with Gentamicin. Moreover, 9a exhibited the best cytotoxic activity against each of HEPG2 and MCF-7 cell lines with IC₅₀ values of 25.7 and 30.53?µM, respectively, when compared with Doxorubicin. The in-silico study was performed to predict the capability of new thienopyridines as potential inhibitors of pim-1 kinase.