Construction and performance characteristics of new tetramisole selective plastic membrane electrodes

New tetramisole (Tm) ion selective PVC membrane electrodes are constructed based on either the ion-pair complex Tm TPB (Electrode I) where TPB is tetraphenylborate or the ion associate Tm(3) PT (Electrode II) where PT is phosphotungstate. The rectilinear concentration ranges of Electrodes I and II are 4 x 10(-5)-10(-2)M (average slope = 55.7 mV/concentration decade) and 5 x 10(-5)-10(-2)M TmCl (average slope = 57.0 mV/concentration decade), at 25 degrees C, respectively. The life time of the two Electrodes I and II are 14 and 49 days of continuous working, respectively. The change in pH does not affect the electrodes performance within the range 3.0-5.5, 3.0-6.0 and 3.0-7.0 for Tm concentrations 10(-2) 5 x 10(-3) and 10(-3)M, respectively. The isothermal coefficients of Electrodes I and II are found to be 0.000667 and 0.001164 V/ degrees C, respectively. The electrodes proved to be highly selective for TmCl towards inorganic cations, sugars and amino acids. The standard addition method and potentiometric titration are used to determine Tm in pure solutions and in tetramisole 10% oral solution. Regeneration process for the exhausted Electrodes I and II is applied successfully by soaking them in a solution of NaTPB and PTA, respectively.     

Fluorimetric determination of aminoglycoside antibiotics using lanthanide probe ion spectroscopy

The application of probe ion fluorimetry has succeeded in the microdetermination of six aminoglycoside antibiotics: neomycin, streptomycin, gentamicin, tobramycin, amikacin and kanamycin as sulfate salts in pure form and in some pharmaceutical preparations. The method is based on the reaction of Eu³⁺ ions with aminoglycosides through amino and hydroxy groups. Such interactions enhance the intensity of the 616 nm fluorescence emission of the Eu³⁺ ion. The fluorescence at 592 nm comes from a non-hypersensitive transition and is not affected by the ligand which is bound to the probe ions. The intensity ratio R, defined as I₅₉₂/I₆₁₆ was used to determine the amount of free and bound europium ions. A linear relationship between bound europium ions and aminoglycoside was found within the concentration ranges 20–100 ppm for neomycin, 5–60 ppm for streptomycin, and 10–70 ppm for gentamicin, tobramycin, amikacin, and kanamycin as sulfate salts. The percentage recoveries ranged from 99.22 to 101.07, with standard deviations ranging from ± 1.5 to ± 4.38. The relative stability constants ranged from 5 × 10³ to 2 × 10⁴. The optimum reaction conditions were studied and the results obtained compared favourably with the fluorimetric method using fluorescmine reagent.     

The interaction between polymerization initiators and inhibitors in solutions—VIII. The mechanism of the reaction of azobisisobutyronitrile with p-benzoquinone and chloranil in polar and nonpolar solvents

The reactions of azobisisobutyronitrile (AIBN) with p-benzoquinone (BQ) and chloranil in toluene, chlorobenzene and acetonitrile, have been investigated by isolation and identification of the reaction products. In toluene and chlorobenzene, isobutyroylamino hydroquinone together with tetramethyl dioxazinobenzene are formed in the case of (BQ); the corresponding mono- and dioxazinobenzene derivatives are formed in the case of chloranil. In acetonitrile, however, only polyquinonoid resinous derivatives of the quinones are obtained. The crystalline derivatives as well as the resinous products have no nitrile groups in their structures and the nitrogen atom is directly attached to the parent quinone nucleus. This fact indicates that the radicals from AIBN react with quinones exclusively in the ketenimine form. A mechanism based on the possibility of electron-transfer from the radical to the quinone molecule to form charged species has been suggested. The degree of separation of these species is determined by the polarity of the solvent. Combination of the charged entities produces nuclear-substituted intermediates which may be eventually isolated as hydroquinones or subjected to further radical reactions with the ketenimine substituent to form the oxazinobenzene derivatives. The formation of ether derivatives of hydroquinone and tetrachlorohydroquinone in the reaction of BQ and chloranil with AIBN is accordingly excluded.     

Activated nitriles in heterocyclic synthesis. A novel synthesis of pyrazolo[1,5-a]pyrimidines and pyrano[2,3-c]pyrazoles

Several new pyrazolo[1,5-a]pyrimidines and pyrano[2,3-c]pyrazoles were synthesized viathe reaction of the cinnamonitrile derivatives 1a-c with 5-amino-3-phenylpyrazole ( 1 ), 3-amino-2-pyrazolin-5-one ( 2 ) and 3-amino-1-phenyl-2-pyrazolin-5-one ( 22 ).     

Cerebral mucormycosis: proton MR spectroscopy and MR imaging

Proton magnetic resonance spectroscopy (MRS) was integrated with magnetic resonance imaging (MRI) in the evaluation of a case of cerebral mucormycosis. MRS showed markedly elevated lactate, depleted N-acetyl aspartate and metabolite resonances attributable to succinate and acetate. The spectroscopy profile is essentially similar to that of bacterial abscess but without the commonly seen resonances of the amino acids valine, leucine and isoleucine. Our extensive literature review did not yield any reports of MRS findings on cerebral mucormycosis. MRS prospectively limited the differential diagnoses given the otherwise nonspecific and complex MR imaging findings in our immunosuppressed patient.     

Design,Synthesis, Pharmacodynamic and In Silico Pharmacokinetic Evaluation of Some Novel Biginelli-Derived Pyrimidines and Fused Pyrimidines as Calcium Channel Blockers

Some new pyrimidine derivatives comprising arylsulfonylhydrazino, ethoxycarbonylhydrazino, thiocarbamoylhydrazino and substituted hydrazone and thiosemicarbazide functionalities were prepared from Biginelli-derived pyrimidine precursors. Heterocyclic ring systems such as pyrazole, pyrazolidinedione, thiazoline and thiazolidinone ring systems were also incorporated into the designed pyrimidine core. Furthermore, fused triazolopyrimidine and pyrimidotriazine ring systems were prepared. The synthesized compounds were evaluated for their calcium channel blocking activity as potential hypotensive agents. Compounds 2, 3a, 3b, 4, 11 and 13 showed the highest ex vivo calcium channel blocking activities compared with the reference drug nifedipine. Compounds 2 and 11 were selected for further biological evaluation. They revealed good hypotensive activities following intravenous administration in dogs. Furthermore, 2 and 11 displayed drug-like in silico ADME parameters. A ligand-based pharmacophore model was developed to provide adequate information about the binding mode of the newly synthesized active compounds 2, 3a, 3b, 4, 11 and 13. This may also serve as a reliable basis for designing new active pyrimidine-based calcium channel blockers.     

Compounds from the Medicines for Malaria Venture Box Inhibit In Vitro Growth of Babesia divergens,a Blood-Borne Parasite of Veterinary and Zoonotic Importance

Babesiosis is an infectious disease with an empty drug pipeline. A search inside chemical libraries for novel potent antibabesial candidates may help fill such an empty drug pipeline. A total of 400 compounds (200 drug-like and 200 probe-like) from the Malaria Box were evaluated in the current study against the in vitro growth of Babesia divergens (B. divergens), a parasite of veterinary and zoonotic importance. Novel and more effective anti-B. divergens drugs than the traditionally used ones were identified. Seven compounds (four drug-like and three probe-like) revealed a highly inhibitory effect against the in vitro growth of B. divergens, with IC₅₀s ≤ 10 nanomolar. Among these hits, MMV006913 exhibited an IC₅₀ value of 1 nM IC₅₀ and the highest selectivity index of 32,000. The atom pair fingerprint (APfp) analysis revealed that MMV006913 and MMV019124 showed maximum structural similarity (MSS) with atovaquone and diminazene aceturate (DA), and with DA and imidocarb dipropionate (ID), respectively. MMV665807 and MMV665850 showed MMS with each other and with ID. Of note, a high concentration (0.75 IC₅₀) of MMV006913 caused additive inhibition of B. divergens growth when combined with DA at 0.75 or 0.50 IC₅₀. The Medicines for Malaria Venture box is a treasure trove of anti-B. divergens candidates according to the obtained results.     

Highly Sensitive Differential Pulse and Square Wave Voltammetric Methods for Determination of Strontium Ranelate in Bulk and Pharmaceutical Dosage Form

The voltammetric behavior of Strontium Ranelate (SR) was studied using Cyclic (CV), differential pulse (DPV) and square wave (SWV) voltammetry. CV showed two well‐defined, irreversible, diffusion‐controlled anodic peaks using Britton‐Robinson buffer, pH 2.0 at Pencil graphite (PGE), Carbon paste (CPE) and glassy carbon (GCE) electrodes. The peak current‐concentration relationship was rectilinear over the range 1.0–10.0, 1.0–11.25 and 2.5–24.0 µg/mL at PGE, CPE and GCE respectively, with a minimum detectability of 0.17, 0.24 and 0.39 µg/mL for peak 1 and 0.19, 0.27 and 0.51 µg/mL for peak 2. Recoveries showed the high accuracy of the method; 99.8 %, 99.5 % and 99.7 % at PGE, CPE and GCE respectively for peak 1 and 100.1 %, 99.9 % and 99.7 % at PGE, CPE and GCE respectively for peak 2. Hence DPV and SWV were conducted for the quantitative determination of SR in its pure and pharmaceutical dosage form. the method was validated and the results were in good agreement with those obtained from the reported method.     

Synthesis of monofunctional curcumin derivatives, clicked curcumin dimer, and a PAMAM dendrimer curcumin conjugate for therapeutic applications

Curcumin, the primary active ingredient in the spice turmeric, was converted to reactive monofunctional derivatives (carboxylic acid/azide/alkyne). The derivatives were employed to produce a 3 + 2 azide-alkyne "clicked" curcumin dimer and a poly(amidoamine) (PAMAM) dendrimer-curcumin conjugate. The monofunctional curcumin derivatives retain biological activity and are efficient for labeling and dissolving amyloid fibrils. The curcumin dimer selectively destroys human neurotumor cells. The synthetic methodology developed affords a general strategy for attaching curcumin to various macromolecular scaffolds.     

Development of new potentiometric sensors for the determination of proguanil hydrochloride in serum and urine

Potentiometric electrodes were developed for the rapid determination of proguanil hydrochloride in pure samples, pharmaceutical preparations and spiked serum and urine samples using PVC membrane,screen printed(SPE), coated wired(CWE), carbon paste(CPE) and modified carbon paste(MCPE)electrodes based on the ion-exchanger of proguanil with phosphotungestic acid(Pr-PT) as a chemical modifier. The prepared electrodes showed Nernestian slopes of 59.7, 58.1, 58.5, 58.5 and 57.0 for the PVC,SPE, CWE, CPE and MCPE for the proguanil ions in a wide concentration range of 1.0 * 10~(-5)–1.0 * 10~(-2)mol L~(-1) at 25°C with detection limits of 7.94 * 10~(-6), 1.0 * 10~(-5), 1.0 * 10~(-6), 7.07 * 10~(-6) and 2.5 * 10~(-6) mol L~(-1), respectively. The prepared electrodes exhibited high proguanil selectivity in relation to several inorganic ions and sugars and they could be successfully utilized for its determination in pure solutions, pharmaceutical preparations and serum and urine samples using the direct potentiometry and standard addition methods with very good recovery values.