Glucuronide conjugates of Soraprazan (BY359), a new potassium-competitive acid blocker (P-CAB) for the treatment of acid-related diseases

Glucuronide conjugates of Soraprazan (BY359), a potent novel anti-secretory drug (currently in Phase II clinical trials), were not directly accessible synthetically. This was due to the relative instability of Soraprazan under the harsh Lewis acid conditions employed in popular glucuronidation methodologies and a lack of reactivity under alternative, Koenigs-Knorr, coupling conditions. We have now devised a successful synthesis using the novel N-acetylated Soraprazan to access the required glucuronide metabolites on gram scale. Coupling of this novel aglycone with methyl 1-O-trichloroacetimidoyl-2,3,5-tri-O-isobutyryl-α-d-glucopyran-uronate in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) gave the protected glucuronide intermediates. A one-pot two-step deprotection involving hydrolysis of the ester functionalities and removal of the N-acetyl group with alkaline hydrazine delivered the title compounds in satisfactory yield.     

Bioactive principles,anti-diabetic,and anti-ulcer activities of Ducrosia anethifolia Boiss leaves from the Hail region,Saudi Arabia

This work aimed to identify the bioactive constituents of Ducrosia anethifolia Boiss eaves through cold methanolic extract. The GC–MS study of cold methanolic extract showed the presence of various pharmaceutically important bioactive compounds with unique peaks at specified retention time. The significant compounds are α-linoleic acid, α-sitosterol, n-hexadecanoic acid, palmitic acid β-monoglyceride, 2-methoxy-4-vinylphenol and benzoic acid, methyl ester. The FT-IR study showed them fingerprint region at 3326.80, 2943.53, 2831.74, 1450, 1110.67 and 1020.80 cm^?1. The FT-IR study suggested the presence of glycosides, flavonoids, tannins, steroids, saponins, fatty acids and squalene. Oral administration of Ducrosia anethifolia Boiss leaves powder (DLP) (100 mg/kg body weight) was successfully reduced the blood sugar level after 14 d treatment in STZ (50 mg/kg bodyweight) induced diabetic rats significantly from 327.93 ± 24.5 to 171 0.03 ± 3.78 mg/dL. Furthermore, DLP (400 mg/kg body weight) was showed 74 ± 1.9 % inhibition of ulcer. The results of this study showed that DLP has both anti-diabetic and anti-ulcer characteristics when tested in vivo.     

Anti-ulcer activity of Smithia conferta in various animal

Smithia conferta Sm. (Leguminasae), is a commonly used plant in Indian traditional medicine. In the current study anti-ulcer activity of its petroleum ether, alcohol and aqueous extracts of leaves were investigated using different animal models. All extracts were also subjected to phytochemical analysis and their toxic potential. Petroleum ether extract was found to contain steroids; alcohol extract revealed the presence of isoflavonoids, alkaloids and carbohydrates; while aqueous extract was found to contain amino acids, carbohydrates and flavonoids. S. conferta aqueous and alcoholic extracts were found to be non-toxic up to 5000 mg/kg dose level while petroleum ether extract was safe only up to a dose of 2000 mg/kg after single dose administration of the extracts.During confirmation of the claimed anti-ulcer activity, treatment with aqueous and alcoholic extracts showed significant reduction in ulcer index, free acidity as well as total acidity in pylorus ligated rats. However, petroleum ether extract showed relatively less profound reduction in all these indices. The anti-ulcer activity observed in aqueous extract treatment group was nearly equivalent to the standard group.     

Development,In-Vitro Characterization and Preclinical Evaluation of Esomeprazole-Encapsulated Proniosomal Formulation for the Enhancement of Anti-Ulcer Activity

Objective: The present study aimed to develop and optimize esomeprazole loaded proniosomes (EZL-PNs) to improve bioavailability and therapeutic efficacy. Method: EZL-PNs formulation was developed by slurry method and optimized by 33 box-Bhekhen statistical design software. Span 60 (surfactant), cholesterol, EZL concentration were taken as independent variables and their effects were evaluated on vesicle size (nm), entrapment efficiency (%, EE) and drug release (%, DR). Furthermore, optimized EZL-PNs (EZL-PNs-opt) formulation was evaluated for ex vivo permeation, pharmacokinetic and ulcer protection activity. Result: The EZL-PNs-opt formulation showed 616 ± 13.21 nm of vesicle size, and 81.21 ± 2.35% of EE. EZL-PNs-opt exhibited negative zeta potential and spherical confirmed scanning electron microscopy. EZL-PNs-opt showed sustained release of EZL (95.07 ± 2.10% in 12 h) than pure EZL dispersion. The ex-vivo gut permeation result exhibited a significantly (p < 0.05) enhanced flux than pure EZL. The in vivo results revealed 4.02-fold enhancement in bioavailability and 61.65% protection in ulcer than pure EZL dispersion (43.82%). Conclusion: Our findings revealed that EZL-PNs formulation could be an alternative delivery system of EZL to enhance oral bioavailability and antiulcer activity.     

Determination of antihypertensive and anti-ulcer agents from surface water with solid-phase extraction-liquid chromatography-electrospray ionization tandem mass spectrometry

Pharmaceuticals are emerging contaminants in surface water and they must be measured to follow their effects on the aquatic environment. We developed a solid-phase extraction and liquid chromatography-electrospray ionization tandem mass spectrometry (SPE-LC-ESI-MS/MS) method for the determination of twenty-six pharmaceutical compounds - which belong to antihypertensive and anti-ulcer agents - from surface water samples. The selection of pharmaceuticals was based on usage frequency in Hungary. During method development Oasis HLB, SampliQ Polymer SCX and Si-SCX SPE cartridges were tested. As LC eluent ammonium formate, ammonium acetate buffers at pH 3 and 5 were investigated and for quantitation both matrix-matched and internal standard calibration was used. For matrix effect assessment post-extraction spike method was applied which can separate the extraction efficiency from ion suppression for better determination of recovery. Method detection limits (MDLs) varied between 0.2 and 10 ng/L. Precision of the method, calculated as relative standard deviation (RSD), ranged from 0.2 to 14.6% and from 1.2 to 22.4% for intra- and inter-day analysis, respectively. The method was applied to analyze Danube water samples. Measured average concentrations varied between 2 and 39 ng/L for eleven compounds and another one could be detected under LOQ.     

Microwave assisted green synthesis of Fe@Au core–shell NPs magnetic to enhance olive oil efficiency on eradication of helicobacter pylori (life preserver)

Eco friendly and green synthetic approach for the synthesis of metallic nanoparticles gained much importance in the recent era. In the present study, an environmental friendly and plant mediated synthetic approach was used for the synthesis of gold coated iron (Fe@Au) nanoparticles using extract solution of olive oil, licorice root (Glycyrrhiza glabra) and coconut oil (OLC). These extracts were acted as a reducing agent during the formation of core–shell nanoparticles that provides long-time stability, lower toxicity and higher permeability to specific target cells. In order to achieve the small sized, regular spherical shaped, and homogeneous nanoparticles optimum conditions were ensured. In fact, the use of microwave irradiation was offered higher reaction rate and better product. The Fe@AuNPs have been characterized by UV–Visible spectroscopy, Energy dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), High resolution Transmission electron microscope (HR-TEM), Fourier Transform Infrared Spectroscopy (FT-IR), high-performance liquid chromatography (HPLC), High angle annular dark-field scanning transmission electron microscopy (HAADF-STEM), Particle-Size Distribution (PSD), and Magnetic hysteresis loops. The synthesized gold coated iron nanoparticles showed significant antioxidant potential with maximum inhibition rates, the biosynthesized nanoparticles were also found effective against Helicobacter pylori (H. pylori) and ulcer.