Fast detection of sildenafil in adulterated commercial products using differential scanning calorimetry

Adulteration of drugs is a serious issue and can have a great impact on human health. It is mainly done with the intention of boosting the effects of products. For many years, the enforcement officers in Malaysia have had difficulty deciding whether some products should be confiscated as they have not been able to produce fast reliable evidence of adulteration. For that reason, we explored the use of differential scanning calorimetry (DSC) as a potential fast detection method of commercial products marketed in Malaysia that may be adulterated. We confirmed the outcomes qualitatively with high pressure liquid chromatography. DSC was set at a heating rate of 10 °C min^?1 and within a temperature range of 100–250 °C with nitrogen as a purge gas at a flow rate of 20 mL min^?1 to analyse a sildenafil reference standard (RS), sildenafil tablets and sildenafil adulterated commercial products. Four sildenafil adulterated commercial products were analysed. Since the melting point of sildenafil in the mixture tended to shift, the presence of sildenafil in three of these adulterated commercial products was confirmed using the spiking method and was re-analysed using DSC. The re-analysed results indicated that the enthalphy of fusion (?H) and the resolution peak of sildenafil increased accordingly depending upon the amount of spiked sildenafil RS. Apart from these results, the DSC curves also showed different patterns for sildenafil RS and the mixtures. Therefore, we concluded that DSC can potentially be used to detect sildenafil in adulterated commercial products.     

Locating saddle points of any index on potential energy surfaces by the generalized gentlest ascent dynamics

The system of ordinary differential equations for the method of the gentlest ascent dynamics (GAD) is tested to determine the saddle points of the potential energy surface of some molecules. The method has been proposed earlier [E and Zhou in Nonlinearity 24:1831 (2011)]. We additionally use the metric of curvilinear internal coordinates. By a number of examples, we explain the possibilities of a GAD curve; it can find the transition state of interest by a gentlest ascent, directly or indirectly, or not. A GAD curve can be a model of a reaction path, if it does not contain a turning point for the energy. We further discuss generalized GAD formulas for the search of saddle points of a higher index. We calculate diverse examples.     

Photodynamic Activity on Biofilm in Endotracheal Tubes of Patients Admitted to an Intensive Care Unit

Ventilator-associated pneumonia (VAP) is an infection that arises after endotracheal intubation affecting patients under intensive care. The presence of the endotracheal tube (ETT) is a risk factor since it is colonized by multispecies biofilm. Antimicrobial photodynamic therapy (aPDT) could be a strategy to decontaminate ETTs. We verify if methylene blue (MB) associated with external illumination of the ETT could be an alternative to destroy biofilm. We performed an in vitro and ex vivo study. In vitro study was performed with P. aeruginosa biofilm grew over ETT for 7 days. After treatment, the surviving cells were cultured for 3 days and the biofilm was analyzed by crystal violet absorbance. Ex vivo study employed ETT obtained from extubated patients. aPDT was performed with MB (100 µm ) and red LED (λ = 640±20 nm). We quantified the biofilm thickness and used scanning electron microscopy and fluorescence technique to verify morphological and functional changes after aPDT. Our results showed that bacteria remain susceptible to aPDT after sequential treatments. We also attested that aPDT can reduce biofilm thickness, disrupt biofilm attachment from ETT surface and kill microbial cells. These data suggest that aPDT should be investigated to decrease VAP incidence via ETT decontamination.     

Terroir Effect on the Phenolic Composition and Chromatic Characteristics of Mencía/Jaen Monovarietal Wines: Bierzo D.O. (Spain) and Dão D.O. (Portugal)

‘Mencía’/‘Jaen’ it’s an important red grape variety, exclusive of the Iberian Peninsula, used in wine production namely in Bierzo D.O. and Dão D.O., respectively. This work evaluates the effect of the two different “terroirs” on the phenolic composition and chromatic characteristics of ‘Mencía’/‘Jaen’ monovarietal wines produced at an industrial scale in the same vintage. Using Principal Component Analysis (PCA), Partial Least Squares-Discrimination Analysis (PLS-DA), and Orthogonal PLS-DA (OPLS-DA) it was found that peonidin-3-coumaroylglucoside, petunidin-3-glucoside, malvidin-3-coumaroylglucoside, peonidin-3-glucoside, malvidin-3-acetylglucoside, malvidin-3-glucoside, and ferulic acid were the phenolic compounds with the highest differences between the two regions. PLS regression allowed to correlate the differences in lightness (L*) and redness (a*) of wines from ‘Jaen’ and ‘Mencía’ to differences in colored anthocyanins, polymeric pigments, total pigments, total anthocyanins, cyanidin-3-acetylglucoside, delphinidin-3-acetylglucoside, delphinidin-3-glucoside, peonidin-3-coumaroylglucoside, petunidin-3-glucoside and malvidin-3-glucoside in wines, and the colorless ferulic, caffeic, and coutaric acids, and ethyl caffeate. The wines a* values were more affected by colored anthocyanins, ferulic acid, total anthocyanins, delphinidin-3-acetylglucoside, delphinidin-3-glucoside and petunidin-3-acetylglucoside, and catechin. The positive influence of ferulic acid in the a* values and ferulic, caffeic, coutaric acids, and ethyl caffeate on the L* values can be due to the co-pigmentation phenomena. The higher dryness and lower temperatures during the September nights in this vintage might explain the differences observed in the anthocyanin content and chromatic characteristics of the wines.     

Flow-through amperometric methods for detection of the bioactive compound quercetin: performance of glassy carbon and screen-printed carbon electrodes

Journal of Solid State Electrochemistry - Rapid methods using batch injection analysis (BIA) with amperometric detection were developed for the determination of quercetin extracted from the...     

A Promising Thermodynamic Study of Hole Transport Materials to Develop Solar Cells: 1,3-Bis(N-carbazolyl)benzene and 1,4-Bis(diphenylamino)benzene

The thermochemical study of the 1,3-bis(N-carbazolyl)benzene (NCB) and 1,4-bis(diphenylamino)benzene (DAB) involved the combination of combustion calorimetric (CC) and thermogravimetric techniques. The molar heat capacities over the temperature range of (274.15 to 332.15) K, as well as the melting temperatures and enthalpies of fusion were measured for both compounds by differential scanning calorimetry (DSC). The standard molar enthalpies of formation in the crystalline phase were calculated from the values of combustion energy, which in turn were measured using a semi-micro combustion calorimeter. From the thermogravimetric analysis (TGA), the rate of mass loss as a function of the temperature was measured, which was then correlated with Langmuir’s equation to derive the vaporization enthalpies for both compounds. From the combination of experimental thermodynamic parameters, it was possible to derive the enthalpy of formation in the gaseous state of each of the title compounds. This parameter was also estimated from computational studies using the G3MP2B3 composite method. To prove the identity of the compounds, the ¹H and ¹³C spectra were determined by nuclear magnetic resonance (NMR), and the Raman spectra of the study compounds of this work were obtained.     

Development of Phenothiazine Hybrids with Potential Medicinal Interest: A Review

The molecular hybridization approach has been used to develop compounds with improved efficacy by combining two or more pharmacophores of bioactive scaffolds. In this context, hybridization of various relevant pharmacophores with phenothiazine derivatives has resulted in pertinent compounds with diverse biological activities, interacting with specific or multiple targets. In fact, the development of new drugs or drug candidates based on phenothiazine system has been a promising approach due to the diverse activities associated with this tricyclic system, traditionally present in compounds with antipsychotic, antihistaminic and antimuscarinic effects. Actually, the pharmacological actions of phenothiazine hybrids include promising antibacterial, antifungal, anticancer, anti-inflammatory, antimalarial, analgesic and multi-drug resistance reversal properties. The present review summarizes the progress in the development of phenothiazine hybrids and their biological activity.     

Experimental and Theoretical Investigation on the Thermochemistry of 3-Methyl-2-benzoxazolinone and 6-Nitro-2-benzoxazolinone

The determination of the reliable thermodynamic properties of 2-benzoxazolinone derivatives is the main goal of this work. Some correlations are established between the energetic properties determined and the structural characteristics of the title compounds, and the reactivity of this class of compounds is also evaluated. Static-bomb combustion calorimetry and high-temperature Calvet microcalorimetry were used to determine, respectively, the standard molar enthalpies of formation in the solid state and the standard molar enthalpies of sublimation, both at T = 298.15 K. Using the results obtained for each compound, the respective gas-phase standard molar enthalpy of formation was derived. High-level quantum chemical calculations were performed to estimate the same property and the results evidence good accordance. Moreover, the gas-phase relative thermodynamic stability of 2-benzoxazolinone derivatives was also evaluated using the respective gas-phase standard molar Gibbs energy of formation. In addition, the relationship between the energetic and structural characteristics of the benzoxazolinones is presented, evidencing the enthalpic increments associated with the presence of a methyl and a nitro groups in the molecule, and this effect is compared with similar ones in other structurally related compounds.     

Recent Progress in the Development of Indole-Based Compounds Active against Malaria,Trypanosomiasis and Leishmaniasis

Human protozoan diseases represent a serious health problem worldwide, affecting mainly people in social and economic vulnerability. These diseases have attracted little investment in drug discovery, which is reflected in the limited available therapeutic arsenal. Authorized drugs present problems such as low efficacy in some stages of the disease or toxicity, which result in undesirable side effects and treatment abandonment. Moreover, the emergence of drug-resistant parasite strains makes necessary an even greater effort to develop safe and effective antiparasitic agents. Among the chemotypes investigated for parasitic diseases, the indole nucleus has emerged as a privileged molecular scaffold for the generation of new drug candidates. In this review, the authors provide an overview of the indole-based compounds developed against important parasitic diseases, namely malaria, trypanosomiasis and leishmaniasis, by focusing on the design, optimization and synthesis of the most relevant synthetic indole scaffolds recently reported.