Synthesis of Pyrano,Pyrido, Oxazino,and Spiro Pyrazole Derivatives and Their Antimicrobial Activity

Russian Journal of Organic Chemistry - Condensation of 5-methyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one with 4-hydroxybenzaldhyde in alcoholic sodium hydroxide yielded...     

Fermionic Coherent States in Optical Lattice

We discuss the coherent state of an attractive superfluid Fermi gas. In order to explain the time evolution of the Fermi atomic gas in the optical lattice, we present mathematical relations for the autocorrelation function and first-order correlation function. The analytical results show a dependence of the oscillation time on the controlling parameters, which may be achieved experimentally.     

Ameliorative Effect of Structurally Divergent Oleanane Triterpenoid, 3-Epifriedelinol from Ipomoea batatas against BPA-Induced Gonadotoxicity by Targeting PARP and NF-κB Signaling in Rats

The pentacyclic triterpenoids (PTs) of plant origin are reputed to restrain prostate cancer (PCa) cell proliferation. This study aims to assess 3-epifriedelinol (EFD) isolated from aerial part of Ipomoea batatas against PCa and its potential mechanism, in vitro and in vivo. Molecular docking affirms good binding affinity of the compound with target proteins exhibiting binding energy of −7.9 Kcal/mol with BAX, −8.1 Kcal/mol (BCL-2), −1.9 Kcal/mol (NF-κB) and −8.5 Kcal/mol with P53. In the MTT assay, EFD treatment (3–50 µM) showed a significant (p < 0.05 and p < 0.01) dose and time dependent drop in the proliferative graph of DU145 and PC3, and an upsurge in apoptotic cell population. EFD displayed substantial IC50 against DU145 (32.32 ± 3.72 µM) and PC3 (35.22 ± 3.47 µM). According to Western blots, EFD administration significantly enhanced the cleavage of caspases and PARP, elevated BAX and P53 and decreased BCL-2 and NF-κB expression, thereby triggering apoptosis in PCa cells. When male Sprague Dawley rats were intoxicated with Bisphenol A (BPA), an apparent increase in prostate mass (0.478 ± 0.08 g) in comparison to control (0.385 ± 0.03 g) indicates prostatitis. Multidose treatment of EFD (10 mg/kg) significantly reduced prostate size (0.404 ± 0.05 g). EFD exhibited substantial curative potential in vivo, as hematological, hormonal and histopathological parameters have been significantly improved. Reduced peroxidation (TBARS), and suppression of inflammatory markers i.e., NO, IL-6 and TNF-α, signposts substantial antiinflammatory potential of the compound. Overall, EFD has shown better binding affinity with target molecules, acceptable ADMET profile, potent antiproliferative and apoptotic nature and significant reduction in inflamed prostate mass of rats. The present study demonstrates acceptable physicochemical and pharmacokinetic properties of the compound with excellent drugable nature, hence EFD in the form of standardized formulation can be developed as primary or adjuvant therapy against PCa and toxins-induced gonadotoxicity.     

Synthesis of patterned polymer brushes from flexible polymeric films

Surface-initiated polymerizations were carried out from polymeric surfaces of commercially important polyester films, poly(ethylene terephthalate) (PET) and poly(ethylene naphthalate) (PEN). These plastic films were modified prior to polymerization by plasma oxidation, exposing surface hydroxyl groups, in order to immobilise patterned self assembled monolayers (SAMs) of trichlorosilane initiator, through the soft lithographic method of microcontact printing (μCP). Subsequently, polymerizations were initiated from the surface via controlled atom transfer radical polymerization (ATRP), under aqueous conditions, to create patterned brushes of the thermo-responsive polymer poly(N-isopropyl acrylamide) (PNIPAM). By creating patterned, rather than homogeneous brushes characterization was made possible by atomic force microscopy (AFM).     

Development and Characterization of Liposome‐Based Formulation of Amiloride Hydrochloride

Amiloride hydrochloride, a generally used diuretic recently has been found effective in the treatment of epilepsy. The side effects of the drug, such as hyperkalemia, hypertension, and hyperaldosteronism were controlled by reducing the dose and targeting the drug to the brain. The objective of this study was to determine the factors influencing encapsulation of amiloride hydrochloride in liposomes and to demonstrate the anti‐epileptic potential of liposomal drug. A series of liposomal formulations of amiloride hydrochloride were prepared by varying the compositions of the formulations. The optimized formulation consisted of 10 mg/mL of amiloride hydrochloride, L‐phosphatidyl choline, lecithin, cholesterol, and butylated hydroxy toulene. The percentage entrapment efficiency in the optimized formulation was 44%. The drug to lipids ratio and L‐phosphatidyl choline: lecithin: cholesterol: butylated hydroxy toulene ratios were 2.0:3.0 and 5:5:5:2, respectively. The formulation showed an in vitro release of 98.17% in 8 hours, and the best fit kinetic model was Peppas model. Treatment with amiloride hydrochloride liposomes resulted in a significant increase in seizure threshold as compared to free drug in increasing current electroshock seizures in mice, which indicated an increase in CNS uptake of drug in liposome formulation.     

Development and validation of a rapid and sensitive UPLC–MS/MS assay for simultaneous quantification of paclitaxel and cyclopamine in mouse whole blood and tissue samples

The prominent stromal compartment surrounds pancreatic ductal adenocarcinoma and protects the tumor cells from chemo‐ or radiotherapy. We hypothesized that our nano formulation carrying cyclopamine (CPA, stroma modulator) and paclitaxel (PTX, antitumor agent) could increase the permeation of PTX through the stromal compartment and improve the intratumoral delivery of PTX. In the present study a sensitive, reliable UPLC–MS/MS method was developed and validated to quantify PTX and CPA simultaneously in mouse whole blood, pancreas, liver and spleen samples. Docetaxel was used as the internal standard. The method demonstrated a linear range of 0.5–2000 ng/mL for whole blood and tissue homogenates for both PTX and CPA. The accuracy and precision of the assay were all within ±15%. Matrix effects for both analytes were within 15%. Recoveries from whole blood, liver, spleen and pancreas homogenates were 92.7–105.2% for PTX and 72.8–99.7% for CPA. The stability was within ±15% in all test biomatrices. The validated method met the acceptance criteria according to US Food and Drug Administration regulatory guidelines. The method was successfully applied to support a pharmacokinetic and biodistribution study for PTX and CPA in mice biomatrices.     

Thermal stability and degradation behavior of novel wholly aromatic azopolyamide-hydrazides

Thermal stability and degradation behavior of a series of novel wholly aromatic polyamide-hydrazides containing azo groups in their main chains have been investigated in nitrogen and in air atmospheres using differential scanning calorimetry (DSC), thermogravimetry (TG), infrared spectroscopy (IR) and elemental analysis. The influences of controlled structural variations and molecular weight on the thermal stability and degradation behavior of this series of polymers have also been studied. The structural differences were achieved by varying the content of para- and meta-substituted phenylene rings incorporated within this series. Azopolyamide-hydrazides having different molecular weights of all para-substituted phenylene type units were also examined. The polymers were prepared by a low temperature solution polycondensation reaction of p-aminosalicylic acid hydrazide [PASH] and an equimolar amount of 4,4′-azodibenzoyl chloride [4,4′ADBC] or 3,3′-azodibenzoyl chloride [3,3′ADBC] or mixtures of various molar ratios of 4,4′ADBC and 3,3′ADBC in anhydrous N,N-dimethyl acetamide [DMAc] containing lithium chloride as a solvent at −10 °C. All the polymers have the same structural formula except the mode of linking phenylene units in the polymer chain. The results clearly reveal that these polymers are characterized by high thermal stability. Their weight loss occurred in three distinctive steps. The first was small and assigned to the evaporation of absorbed moisture. The second was appreciable and was attributed to the cyclodehydration reaction of the hydrazide groups into 1,3,4-oxadiazole rings by losing water, combined with elimination of azo groups by losing molecular nitrogen. This is not a true degradation but rather a thermo-chemical transformation reaction of the azopolyamide-hydrazides into the corresponding polyamide-1,3,4-oxadiazoles. The third was relatively severe and sharp, particularly in air, and corresponded to the decomposition of the resulting polyamide-1,3,4-oxadizoles. In both degradation atmospheres, the improved resistance to high temperatures was always associated with increased content of para-phenylene moieties of the investigated polymer. The better thermal stability of the wholly para-oriented type of polymer relative to the other polymers is attributed to its greater chain symmetry which is responsible for its greater close packing, rod-like structure and consequently stronger intermolecular bonds which would be more difficult to break and therefore more resistance to high temperatures. Further, with exception of 160-200 °C temperature range, where the lower molecular weight samples showed considerable weight losses which were most probably due to hydrogen bonded DMAc, all the wholly para-oriented phenylene type of polymer samples behaved similarly regardless of their respective molecular weight. This seems to indicate that the structural building units responsible for high thermal stability of the polymers are their characteristic groups, such as aromatic moieties, amide and hydrazide linkages in case of azopolyamide-hydrazides, and 1,3,4-oxadiazole rings, aromatic nuclei and amide linking bonds in case of polyamide-1,3,4-oxadiazoles, rather than the longer chain segments.     

Bioinspired NC Coated BM-ZIF for Electrochemical Monitoring of Adrenaline from Blood and Pharmaceutical Samples

Herein, we have developed highly sensitive and selective non-enzymatic bioinspired polydopamine derived nitrogen rich carbon (NC) coated bimetallic zeolitic imidazolate framework (BM-ZIF) electrochemical sensor via simple hydrothermal approach for monitoring adrenaline (AD) from COVID-19 quarantined person blood and pharmaceutical sample. The designed NC-BM-ZIF electrode shows excellent sensitive and selective performance towards AD monitoring with detection limit (LOD) of 0.01 nM and 0.1931 μA/nM/cm² sensitivity over a wide linear range of 50–1625 nM. To the best of our knowledge, this is the first study of using of NC-BM-ZIF electrode for the electrochemical sensing of AD from quarantined person blood and pharmaceutical sample.     

Mechanistic study of hydrolytic erosion and drug release behaviour of PLGA nanoparticles: Influence of chitosan

The hydrolytic erosion of poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (PLGA-NPs) was investigated in vitro. The changes in physical properties of the nanoparticles with time were evaluated by ultra high-pressure liquid chromatographic (UHPLC) analysis, particle size analysis and scanning electron microscopy (SEM). Mass reduction data demonstrated a triphasic erosion pattern for PLGA-NPs with nearly no mass loss (3.0%) up to a week, followed by a rapid mass loss (weeks 1-3, 61.4%), and further followed by slow mass loss (weeks 3-5, 19.8%). SEM revealed microcavitation on the surface of nanoparticles, which tended to increase with the erosion time and eventually particle fragmentation was evident at 5 weeks. A significant increase in particle size was observed at 4 weeks which can be attributed to particle aggregation, however, at about 5 weeks, the particle size decreased significantly owing to particle fragmentation. The hydrolytic erosion of PLGA-NPs was found to be specifically proton catalyzed. The release profile of the model drug, moxifloxacin, from PLGA-NPs was closely related to nanoparticle erosion except for the initial burst release which was based on diffusion. The presence of chitosan in the PLGA-NPs accelerated the rate of erosion of the nanoparticles and reduced the burst release of the drug. An understanding of the erosion mechanism and alteration in erosion by chitosan could give desirable and more uniform drug release kinetics from PLGA-NPs.     

The Involvement of l-Arginine-Nitric Oxide-cGMP-ATP-Sensitive K+ Channel Pathway in Antinociception of BBHC,a Novel Diarylpentanoid Analogue,in Mice Model

The present study focuses on the possible involvement of l-arginine-nitric oxide-cGMP-ATP-sensitive K⁺ channel pathway in the antinociceptive activity of a novel diarylpentanoid analogue, 2-benzoyl-6-(3-bromo-4-hydroxybenzylidene)cyclohexen-1-ol (BBHC) via a chemical nociceptive model in mice. The antinociceptive action of BBHC (1 mg/kg, i.p.) was attenuated by the intraperitoneal pre-treatment of l-arginine (a nitric oxide synthase precursor) and glibenclamide (an ATP-sensitive K⁺ channel blocker) in acetic acid-induced abdominal constriction tests. Interestingly, BBHC’s antinociception was significantly enhanced by the i.p. pre-treatment of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a selective inhibitor of soluble guanylyl cyclase (p < 0.05). Altogether, these findings suggest that the systemic administration of BBHC is able to establish a significant antinociceptive effect in a mice model of chemically induced pain. BBHC’s antinociception is shown to be mediated by the involvement of l-arginine-nitric oxide-cGMP-ATP-sensitive K⁺ channel pathway, without any potential sedative or muscle relaxant concerns.