Synthesis, Reactions, and Anti-arrhythmic activity of Substituted Heterocyclic Systems Using 5-Chloroanisic Acid as Starting Material

Summary. A series of substituted heterocyclic systems were prepared from N1-[4-(4-fluorocinnamoyl)phenyl]-5-chloro-2-methoxybenzamide, which was prepared from the corresponding 5-chloroanisic acid (2-methoxy-4-chlorobenzoic acid) as starting material. Treating of the cinnamoyl derivative with hydrazine hydrate in dioxane afforded a pyrazoline, which was reacted with morpholine and paraformaldehyde to give the N-substituted pyrazoline. Acylation of pyrazoline with acetyl chloride in dioxane afforded the N-acetyl analogue. Also, the cinamoyl derivative was reacted with methylhydrazine, phenylhydrazine, or ethyl cyanoacetate to yield the corresponding N-methyl-, N-phenylpyrazoline, pyrane, and pyridone derivatives. Condensation of the cinnamoyl derivative with cyanothioacetamide gave the pyridinethione derivative, which was treated with ethyl chloroacetate affording the ethyl carboxylate derivative. Also, it was reacted with malononitrile or ethyl acetoacetae to give the cyano amino analougues and ethyl carboxylate, which was reacted with methylhydrazine to give the (indazolyl)phenyl derivative. On the other hand, reaction of cinnamoyl derivative with acetyl acetone afforded the cyclohexenyl derivative, which was reacted with hydrazine hydrate to give the [methylindazolyl]phenyl derivative. Condensation of the cinnamoyl derivative with guanidine hydrochloride or thiourea afforded the aminopyrimidine derivative and thioxopyrimidine. The latter was condensed with chloroacetic acid to yield a thiazolopyrimidine, which was condensed with 2-thiophenealdehyde to yield the arylmethylene derivative, however, it was also prepared directly from thiopyrimidine by the action of chloroacetic acid, 2-thiophenealdehyde, and anhydrous sodium acetate. The pharmacological screening showed that many of these compounds have good anti-arrhythmic activity and low toxicity.     

Synthesis and antiinflammatory activity of some pyrimidines and thienopyrimidines using 1-(2-Benzo[d][1,3]dioxol-5-yl)vinyl)-4-mercapto-6-methylpyrimidine-5-yl)ethan-2-one as a starting material

In continuation to our search for new heterocyclic systems based antiinflammatories, the suggestion and synthesis of some pyrimidines, thienopyrimidines, and their derivatives, were herein realized. The pharmacological screening showed that many of these compounds have good antiinflammatory activity. The structure assignments of the new compounds are based on chemical and spectroscopic evidence. The detailed synthesis, spectroscopic data, and pharmacological properties are reported. Correspondence: Abd El-Galil Elsayed Amr, National Research Center, Organic Chemistry Department, Cairo, Dokki, Egypt.     

The vibro-acoustic response and analysis of a full-scale aircraft fuselage section for interior noise reduction

The surface and interior response of a Cessna Citation fuselage section under three different forcing functions (10-1000 Hz) is evaluated through spatially dense scanning measurements. Spatial Fourier analysis reveals that a point force applied to the stiffener grid provides a rich wavenumber response over a broad frequency range. The surface motion data show global structural modes (approximately < 150 Hz), superposition of global and local intrapanel responses (approximately 150-450 Hz), and intrapanel motion alone (approximately > 450 Hz). Some evidence of Bloch wave motion is observed, revealing classical stop/pass bands associated with stiffener periodicity. The interior response (approximately < 150 Hz) is dominated by global structural modes that force the interior cavity. Local intrapanel responses (approximately > 150 Hz) of the fuselage provide a broadband volume velocity source that strongly excites a high density of interior modes. Mode coupling between the structural response and the interior modes appears to be negligible due to a lack of frequency proximity and mismatches in the spatial distribution. A high degree-of-freedom finite element model of the fuselage section was developed as a predictive tool. The calculated response is in good agreement with the experimental result, yielding a general model development methodology for accurate prediction of structures with moderate to high complexity.     

Biofouling prevention with pulsed electric fields

Temporary immobilization of aquatic nuisance species through application of short electric pulses has been explored as a method to prevent biofouling in cooling water systems where untreated lake, river, or sea water is used. In laboratory experiments, electrical pulses with amplitudes on the order of kilovolts/centimeter and submicrosecond duration were found to be most effective in stunning hydrazoans, a common aquatic nuisance species. Varying pulse amplitude and repetition rate allows us to control the stunning time in a temporal range from minutes to hours. The temporary immobilization is assumed to be caused by reversible membrane breakdown. This assumption is supported by results of measurements of the energy required for stunning. Based on the data obtained in laboratory experiments, field experiments in a tidal mater environment have been performed. The flow velocity was such that the residence time of the aquatic nuisance species in the system was approximately half a minute. The results showed that the pulsed electric field method provides full protection against biofouling when pulses of 0.77 μs width and 6 kV/cm amplitude are applied to the water at the inlet of such a cooling water system. Even at amplitudes of 1 kV/cm, the protection is still in the 90% range, at an energy expenditure of 1 kWh for the treatment of 60 000 gallons of water     

Promoter Methylation of RASSF1A Gene in Egyptian Patients with Ovarian Cancer

Ovarian malignancy is diagnosed in nearly a fourth of a million women internationally every year. Methylation of RASSF1A tumor suppressor gene prompts its inactivation in diseases. In this study, the RASSF1A promoter methylation was detected by methylated-specific PCR and investigated serum RASSF1A protein level through enzyme-linked immunosorbant assay in 160 Egyptian patients with ovarian cancer and 160 healthy controls. The present work proved that there was a higher frequency of RASSF1A methylation and a decrease in its serum level in patients with ovarian cancer compared to controls as well as in the high-grade tumor patients compared to low grade ones and also in advanced ovarian tumor stage compared to early stages. Our study exhibited that RASSF1A promoter hypermethylation and its protein levels may be a reliable and sensitive tool for diagnosing and monitoring of ovarian malignancy patients.     

SEM-mapped micro-photoluminescence studies of highly luminescent micro-clusters in erbium-doped silicon-rich silicon oxide

This paper reports on the formation of unique micrometer-scale clusters in erbium-doped silicon-rich silicon oxide (ErSRSO) thin films produced by thermal evaporation. Through scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX), we identify these micro-clusters as structures where the film curves away from the substrate to encase erbium-rich aggregates. Even though erbium aggregation has been reported to cause quenching, we demonstrate that the micro-clusters as a whole can exhibit significantly enhanced erbium photoluminescence (PL), with emissions over 24 times brighter than the surrounding non-cluster region. Mapping micro-photoluminescence measurements onto SEM images reveals that the erbium aggregates alone do not generate the enhanced PL, but rather the thin film encasing the aggregates is the origin of the emissions. Analysis of the PL Stark splitting shows a correlation between the micro-clusters’ fine structure and the strength of their PL. Taken together, the above evidence indicates that the micro-clusters’ strong PL is produced by changes in the local environment of the Er³⁺ inside the thin film surrounding the erbium-rich aggregates.     

Design of Copper Microfabricated Potentiometric Sensor for in-line Monitoring of Neostigmine Degradation Kinetics

The quality of pharmaceutical products is critical for human health. Drug development requires tools to assess the presence of degradation products and contaminants during the manufacturing and storage processes. Accelerated stress degradation and kinetic studies play a vital role in predicting final product stability. This work describes the design of potentiometric sensor based on copper microfabricated electrodes for in-line tracking the degradation kinetics of neostigmine. The proposed electrochemical technique provides a continuous profile for the hydrolysis of NEO under different temperatures and pH. The hydrolysis activation energy was found to be 18.88 kcal mol⁻¹ which was aligned with the reported hydrolysable ester values. Consequently, the kinetic data analysis is crucial to predict the optimum analysis and storage conditions.     

Synthesis of Carboxymethyl Cellulose Based Drug Carrier Hydrogel Using Ionizing Radiation for Possible Use as Site Specific Delivery System

A unique natural polymer based colon specific drug carrier was prepared from carboxymethyl cellulose (CMC) and acrylic acid (AAc) in aqueous solution employing γ‐radiation induced copolymerization and crosslinking. The effect of preparation conditions such as the natural polymer content and irradiation dose on gelation process was investigated. The swelling behavior of the prepared hydrogels was characterized by investigating the time and pH dependent swelling of the (CMC/AAc) hydrogels of different CMC content. The effects of the hydrogel composition and pH of the swelling medium on the swelling indices were estimated. The results show that the increment in the CMC content in the feed solution enhances the gelation process. The results also show the dependence of the swelling indices on both hydrogel composition and pH value of the swelling medium. To evaluate the ability of the prepared hydrogel to be used as a colon‐specific drug carrier, the release profile of theophylline was studied as a function of time at pH 1 and pH 7.     

A PVC Membrane Sensor for Potentiometric Determination of Atorvastatin in Biological Samples and Pharmaceutical Preparations

The present article reports for the first time the use of Aliquat 336S‐atorvastatin as an electroactive material in a poly(vinyl chloride) matrix membrane sensor plasticized with ortho‐nitrophenyl‐octylether (o‐NPOE) or dioctylphthalate (DOP) for determination of atorvastatin in biological samples (human plasma) and in pharmaceutical preparations. The sensor shows fast, stable and reproducible response over the concentration range of 1.0×10^?7–1.0×10^?2 mol L^?1 atorvastatin with anionic slopes of 60.94±0.2 and 58.22±0.2 and pH range of 5.0–9.0 for o‐NPOE and DOP plasticized based membrane sensors, respectively. The response time of the sensor is stable and fast (10 s). Results were achieved with average recoveries of 99.5 % and 99.3 % and mean standard deviations of ±1.1 % and ±1.4 % for o‐NPOE and DOP plasticized based membrane sensors, respectively. The sensor exhibits high selectivity towards atorvastatin in the presence of many anions, drug excipients and diluents. Validation of the method according to the quality assurance standards shows suitability of the proposed sensors for use in the quality control assessment of the drug.