On the iodination of eudesminic acid with INO3 in an aqueous methanol medium

INTRODUCTION: Both iodo-substituted aromatic hydrocarbons and their more complex derivatives (phenols, aromatic acids, carbaldehydes, and others) are currently being used with unquestionable success in organic and pharmaceutical synthesis. Rationally, the design of a wide variety of polysubstituted biphenyl, stilbene, and other derivatives can be successfully accomplished using these compounds. As a continuation of our previous work, we propose a much more convenient and feasible methodology for the synthesis of the polysubstituted diiodo-containing 2,6-diiodo-3,4,5-trimethoxybenzoic acid.AIM: The aim of this article is to demonstrate the suitability of the used reagent pair, I2/AgNO3, in the iodination of the natural 3,4,5-trimethoxybenzoic (eudesmic) acid in the presence of water.MATERIALS AND METHODS: For the synthesis of the principal, a green strategy was applied, which used the commonly available and biocompatible reagents iodine, silver nitrate, methanol, and water. The suitability of the applied synthetic methodology was determined by the purity of the reaction product. The latter was established through Fourier transform infrared (FTIR) and 1H nuclear magnetic resonance (NMR) analysis.RESULTS: The presence of a small amount of water in the reaction mixture did not alter the yield and purity of the desired reaction product, 2,6-diiodo-3,4,5-trimethoxybenzoic acid. In all probability, the in situ-formed iodine nitrate (INO3) preserved its activity in an aqueous environment. The quantitative conversion of the organic reactant used can also be taken as indirect evidence of the stability of the thus obtained INO3.CONCLUSION: The presented preparative methodology holds potential as an optimal choice in the synthesis of the target 2,6-diiodo-3,4,5-trimethoxybenzoic acid. Given its feasibility and use of commonly available reagents, the presented synthetic strategy can be easily implemented by novice chemists, including students

Phenothiazine dye labeling test for quinotoxine

INTRODUCTION: Quinotoxine is an alkaloid that was originally obtained synthetically by Pasteur. Its presence in quinine bark was subsequently established. However, numerous biological tests with this alkaloid dispelled all suspicions about its toxicity. Despite this, the suffix -toxin in its trivial name has remained unchanged. In the 1970s, the appearance of this alkaloid was registered on the pharmaceutical market. Over the years, a number of its derivatives, which featured a powerful antibacterial effect, also appeared. Whether it has been regarded as a synthetic precursor or a drug, the potential of the alkaloid in question is undeniable. Therefore, every single aspect of its analysis is fully justified.AIM: The aim of this article is to provide a much handier method for the qualitative analysis of the alkaloid quinotoxine. MATERIALS AND METHODS: A strategy developed by Kehrmann was applied for the qualitative analysis of quinotoxine; this strategy targets the alkaloid’s inherent piperidine residue. All tests were conducted using standard laboratory glassware. The authenticity of the studied alkaloid was confirmed by infrared and ultraviolet visible (UV-Vis) analysis.RESULTS: Immediately following the introduction of the studied alkaloid to the bromine-phenothiazine solution, the appearance of a characteristic blue coloration was registered. To rule out the possibility of a false-positive result, the alkaloid quinine was also analyzed in parity. No indication of any analytical reflex to the quinuclidine-containing alkaloid was observed. The main characteristic of this test, the limit of detection (LOD), was also established. Its value was determined to be 7.5 micrograms.CONCLUSION: This communiqué can be perceived as a first attempt to analyze the piperidine residue of the alkaloid quinotoxine. Given that other available methods target the quinoline residue, which is common to this alkaloid class, the presented test may represent an optimal choice for achieving the intended goal. Moreover, given the feasibility of the presented test, it can be easily implemented and can be performed by student pharmacists

Hydrolytic stability of diltiazem in the presence of chosen polymers - Poloxamer 407 and Ammonio Metacrylate Copolymer Type B (Eudragit RS): а preliminary study

Introduction: The hydrolytic stability of the calcium channel blocker representative diltiazem hydrochloride in the presence of different polymeric entourage was quantitatively assessed using HPLC.Aim: The experiment was performed in order to establish drug-excipients compatibility in Poloxamer 407 hydrogel formulations, where the drug was introduced either by a direct (conventional) approach or in the form of Eudragit RS microsponge-type particles with sustained drug release.Materials and Methods: Samples of conventional diltiazem 2% hydrogel and microsponge-enriched diltiazem 2% hydrogel were stored at 25±2oC for 10 months, protected from light. Analysis of the chemical decomposition rate of diltiazem hydrochloride to its desacetyl degradant - O-desacetyl-diltiazem hydrochloride - was performed in the period between 4th and 10th month of storage.Results and Discussion: It was hypothesized that a polymeric “shield” of Eudragit RS in the composition of diltiazem-loaded porous microspheres and/or the enhanced viscosity achieved by the addition of high-molecular gelling agent Poloxamer 407 to an aqueous drug dispersion will benefit the drug’s stability. Instead, a negative effect on the hydrolysis rate was found to be dominant for both polymers, likely due to an “unfavorable” shift in the dielectric conductivity of the media and/or suspected catalytic effect of quaternary ammonium groups of Eudragit RS.Conclusion: These preliminary results led us to a deeper understanding of the polymeric impact on diltiazem hydrolytic behavior and a very useful foundation for a future preformulation stage in the development of diltiazem modified-release semisolid forms for the treatment of chronic anal fissure

Electrochemical detection of Nitrofural in the presence of sodium amminepentacyanoferrate (II)

The present study deals with the development of a new qualitative electrochemical analytic test for detecting the chemotherapeutic agent Nitrofural. The combination of sodium amminepentacyanoferrate(II) and electric power, provided by a 9V battery, was successfully implemented for the analysis of the medicine in question

A quartz crystal microbalance-assisted method for the assessment of iodine content in organoiodines

Introduction: A new experimental quantitative approach for evaluating iodine content in organoiodine compounds has been proposed, based on the quartz crystal microbalance (QCM) method. This approach relies on following the time behavior of the resonance frequency of the quartz plate under temperature activation of iodine-containing analyte deposited on its surface.Materials and Methods: We have applied the QCM method and the pharmacopoeial titrimetric method.Results and Conclusion: From the mass variations observed, the quantity of emitted iodine is precisely obtained, which readily delivers its initial content in the studied sample. The obtained value corresponds exactly to the theoretical prediction, in contrast to the value obtained by applying the conventional pharmacopoeial metrics

Development of an inkjet calibration phantom for x-ray imaging studies

Introduction: 3D anthropomorphic models of human tissues have become a requirement for conducting realistic virtual studies. One of the current directions in the research of X-ray imaging is the development of physical models with 3D printing techniques using specific materials aiming to obtain replica of the human body tissues with similar radiological characteristics.Aim: The aim of this study is to create a calibration phantom for establishing the X-ray properties of different cartridge infills and their suitability to represent the X-ray properties of different breast types.Materials and Methods: A physical calibration model consisting of 22 objects was designed and printed by using an inkjet printer. A mixture was obtained from 5 mL printer ink and 3 g of potassium iodide (KI), which was used to fill the printer’s cartridge and to print the model on a set of plain office paper. Experimental X-ray images of the physical model were acquired on radiographic system SEDECAL X PLUS LP+. The obtained attenuation coefficient of the printing mixture was evaluated and compared to the breast tissue coefficients corresponding to the used X-ray energy.Results and Discussion: The physical model was printed on ten office sheets and stacked above one another. The obtained attenuation coefficient of the printing mixture was found very similar to that of the glandular tissue of the breast for the used X-ray energy.Conclusion: The obtained printer ink-KI mixture is suitable for representing the glandular part of breast tissue. The method has the potential to be used for creation of a realistic physical breast model

Diltiazem-loaded Eudragit RS 100 microparticles for drug delivery: the challenge of viscosity

Strongly shape-dependent viscosity has been found in drug loaded and `empty` polymeric microspheres (drug delivery systems) made of pharmacopoeial Eudragit RS 100 representative. The dramatically increased viscosity of a layer of spherical particles deposited on the gold electrode surface of quartz resonators from water suspension leads to a large dynamic resistance and inability to sustain stable oscillations in a frequency measuring circuit. The viscosity is also affected by loading the polymer matrix with Diltiazem. Its adverse impact is removed by exposing the deposed layer to acetone vapor leading to `dissolving` the investigated spheres and changing their shape to a thin layered one

Risk Of Development Of Solid Tumors In Patients With Systemic Lupus Erythematosus

Системният лупус еритематозус (СЛЕ) е автоимунно заболяване, характеризиращо се с продуциране на различни автоантитела, активиране на комплемента и отлагане на имунни комплекси. Връзката между СЛЕ и рака отдавна е установена. При пациенти със СЛЕ честотата и рискът от злокачествено заболяване се увеличава за белодробен карцином, рак на шийката на матката, хепатоцелуларен карцином и др. В същото време честотата на карцином на гърдата, на простатната жлеза и яйчниците е ниска в редица проучвания на СЛЕ пациенти.Известни са редица фактори, които могат да допринесат за развитието на злокачествени заболявания при СЛЕ. В този преглед ние представяме някои по-често срещани солидни тумори и тяхната честота при пациенти със СЛЕ, както и факторите, които влияят на туморогенезата в условията на автоимунно заболяване.Systemic lupus erythematosus (SLE) is an autoimmune disease, characterized by production of different autoantibodies, complement activation, and immune complex deposition. An association between SLE and cancer has long been known. In patients with SLE, the incidence and risk of overall malignancy is increased for lung cancer, cervical cancer, liver cancer, and etc. Conversely, the incidences of prostate, breast and ovarial cancers are decreased in a number of studies of SLE patients.There are many factors, which can contribute to the development of malignancies in SLE. In this review we present some more common solid tumors and their incidence in SLE patients as well as the factors that affect tumorigenesis in conditions of autoimmune disease

Convenient method for one-pot synthesis of novel amidotrizoic acid radioisosteres

Introduction: The present study presents an effective one-pot protocol for the synthesis of triiodosubstituted aromatic (benzoic) acids – radiopaque analogues of amidotrizoic acid. For the production of the acids intended, I2/AgNO3 couple was used as an effective iodinating reagent. Moreover, suitably substituted methoxybenzoic acid derivatives were selected as appropriate targets for iodination. The total iodine content in the final (crude) products was determined by Volhard’s titrimetric method. Further details on the chemical structure of the reaction products were obtained by ATR-FTIR and 1H NMR spectroscopy.Aim: The aim of the present study is to evaluate the effectiveness of a new method proposed for the synthesis of triiodo-substituted aromatic acids – analogues of the X-ray contrast amidotrizoic acid.Materials and Methods: All necessary reagents and solvents for the study were purchased from Acros Organics, Fisher. The syntheses were performed under mild conditions using standard laboratory equipment. The infrared (IR) spectral instrument was a TENSOR II of Bruker (Germany), equipped with an ATR (Platinum) attachment. The total iodine content of the crude reaction products was assayed by a classical pharmacopoeial method.Results: All aromatic acids were successfully iodinated with the reagent couple used. Unfortunately, it was found that the reaction products were mixtures of several compounds – partially and completely iodinated products. The presence of 2,6-diodosubstituted acids in them was established by the appearance of a ν(C=O) band in the shortwave range (at over 1700 cm-1). The total iodine content in the final (crude) products was determined by Volhard's back titration method.Conclusion: The applied synthetic method allows the production of a mixture of partially and completely iodinated products, derivatives of the utilized aromatic acids – 3,4-dimethoxybenzoic (3,4-DMBA) and 3,5-dimethoxybenzoic acid (3,5-DMBA). The presence of 2,6-diodosubstituted acids in the products’ composition was determined using ATR FTIR spectroscopy. The reduced yield of the totally substituted products was associated with the lower activity of the iodinating reagent. However, the iodine content of one of the products thus obtained was found to be close to the expected triiodine one