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Micellar liquid chromatography (MLC) has proven beneficial efficiency and ecological impact for routine quality control activities. In the proposed study, cyrene was investigated for the first time, together with other green additives, as a novel safe organic solvent in reversed‐phase MLC. Quality‐by‐design (QbD) approach screened their effect on the separation performance. Six antidiabetic drugs from different classes, namely, metformin (MTF), empagliflozin (EMP), ertugliflozin (ERT), linagliptin (LNT), sitagliptin (SIT), and gliclazide (GCZ) were utilized to assess some newly approved antidiabetic drugs and combinations. An organic solvent‐free mobile phase consisting of (0.01 M Brij‐35, 0.09 M sodium dodecyl sulfate, and 0.01 M ammonium acetate, pH 5.0) separated the studied drugs using an RP‐C18 core–shell column. The flow rate was set at 1.2 mL/min, and analytes were detected using a photodiode array detector at 245, 270, and 225 nm. System suitability parameters demonstrated MLC capability to eliminate organic solvents without compromising separation efficiency. The method was validated across a concentration range of 2.0–30.0 µg/mL for EMP, ERT, and LNT, 20.0–120.0 µg/mL for GCZ and SIT, and 100.0–600.0 µg/mL for MTF. The method successfully determined analytes in different single and multicomponent tablets. Greenness assessment was performed using MoGAPI and AGREE metrics. [ABSTRACT FROM AUTHOR]

Myrrh oleo‐gum‐resin (MOGR) is a natural substance that has a rich history of medicinal use due to its anti‐inflammatory, antimicrobial, and antioxidant properties. The present study reports on the fabrication and assessment of pectin and K‐carrageenan composite films infused with varying proportions (0.3%, 0.5%, and 0.7%) of MOGR. Morphological analysis of the film samples was conducted using Scanning Electron Microscopy (SEM) and Atomic Force Microscopy (AFM). The results indicated that the introduction of MOGR led to a notable increase in surface roughness. The SEM micrographs of the films showed that the MOGR addition had an important effect on the microstructure of the film. The surface hydrophobicity of the MOGR‐loaded films increased, as confirmed by the rise in the contact angle. Moreover, there was an increase in the thickness (0.062 ± 0.004–0.095 ± 0.006 mm) and opacity (1.24 ± 0.07–9.41 ± 0.24) of the films with the addition of MOGR; however, tensile strength (7.30 ± 0.50–4.92 ± 0.34 MPa), elongation at break (32.41% ± 1.0%–29.70% ± 0.24%), and barrier properties decreased. Additionally, a rise in MOGR concentration corresponded to a rise in overall color difference ΔE (0.77 ± 0.03–5.09 ± 0.49) of the films. Notably, the incorporation of MOGR led to an increase in the antioxidant activity of the composite films, indicating potential applications in functional packaging materials. [ABSTRACT FROM AUTHOR]

Objectives: To examine care partner preparedness in caring for recently hospitalized persons with dementia and care partner characteristics associated with preparedness at discharge, 2 months, and 6 months post discharge. Methods: Stepwise regression in a sample of 461 care partners of hospitalized persons with dementia who participated in the Fam‐FFC clinical trial. Results: On average, care partners were 61.81 years old (SD = 14.19) and primarily female (n = 334, 72.5%). Care partners reported having some preparedness in general and it increased from discharge (23.75, SD = 6.78) to 2 months (24.5, SD = 6.49) and 6 months (26.35, SD = 6.73). Multiple care partner characteristics were associated with preparedness at discharge [age (b = −0.071; p < 0.001), burden (b = −0.283; p < 0.001), and depression (b = −0.284; p < 0.01)], 2 months [burden (b = −0.226; p < 0.001), strain (b = −0.144; p < 0.05), depression (b = −0.185; p < 0.05)] and 6 months [burden (b = −0.164; p < 0.01), strain (b = −0.183; p < 0.05), depression (b = −0.279; p < 0.01)] post discharge. While care partners' feelings of greater burden and depression were associated with lower preparedness at all time points, care partners' higher age was associated with lower preparedness at discharge only and care partners' feelings of higher strain was associated with lower preparedness at two and 6 months post discharge. Conclusion: Findings suggest the need to address care partners' feelings of burden, strain, and depression with tailored interventions and programs to optimize their preparedness in meeting unique care needs of hospitalized persons with dementia. Resilience‐based interventions and programs can be useful to manage feelings of burden, strain, and depression and optimize preparedness. [ABSTRACT FROM AUTHOR]

A novel series of benzimidazole hydrazone‐Schiff bases have been prepared through multi‐step reaction process and structurally confirmed by13C‐,1H‐NMR and HR‐MS (ESI) spectroscopic techniques and evaluated against prolyl oligopeptidase (POP) inhibitory activity. In the series, eleven derivatives 20, 14 15, 19, 10, 9, 11, 4, 5, 18, and 21 revealed excellent inhibition potential having IC50 values from (IC50=1.44±0.08 μM) to (IC50=5.66±0.48 μM). However, six out of twenty compounds 12, 16, 13, 17, 22, and 3 attributed significant activity while, three compounds were found good active in the range of IC50 values 10.43±0.57 to 11.45±0.63 μM. The docking studies indicates that the hydrazone moiety show an imperative part in binding with one of the catalytic residues (Arg643) in the substrate binding region of POP enzyme. The excellent inhibitions of these compounds for POP enzyme may lead them to be a good candidates for drug against neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) is considered one of the most common cardiac diseases and major cause of death worldwide. The prevalence of MI and MI‐associated mortality have been increasing in recent years due to poor lifestyle habits viz. residency, obesity, stress, and pollution. Synthetic drugs for the treatment of MI provide good chance of survival; however, the demand to search more safe, effective, and natural drugs is increasing. Plants provide fruitful sources for powerful antioxidant and anti‐inflammatory agents for prevention and/or treatment of MI. However, many plant extracts lack exact information about their possible dosage, toxicity and drug interactions which may hinder their usefulness as potential treatment options. Phytoconstituents play cardioprotective role by either acting as a prophylactic or adjuvant therapy to the concurrently used synthetic drugs to decrease the dosage or relief the side effects of such drugs. This review highlights the role of different herbal formulations, examples of plant extracts and types of several isolated phytoconstituents (phenolic acids, flavonoids, stilbenes, alkaloids, phenyl propanoids) in the prevention of MI with reported activities. Moreover, their possible mechanisms of action are also discussed to guide future research for the development of safer substitutes to manage MI. [ABSTRACT FROM AUTHOR]

In this study, benzoin oleogum resin (BOGR) loaded antioxidant gelatin/pectin (GEPE) based films were developed and characterized for various parameters including mechanical, barrier, optical, film hydrophilicity/hydrophobicity, surface roughness, chemical, thermal, morphological and antioxidant properties. The incorporation of BOGR decreased water solubility, moisture content, tensile strength, and elongation at break. However, water permeability, opacity, thickness, and water hydrophobicity were increased. Moreover, SEM and AFM analysis confirmed that the films loaded with BOGR showed heterogeneous and rougher surfaces in comparison to blank film. The intermolecular interactions between GEPE and BOGR was confirmed by infrared spectroscopy. Thermal stability of the prepared BOGR loaded films was improved. Additionally, antioxidant activities of the film were significantly increased with increase in concentration of BOGR as indicated by ABTS and DPPH assays. Our findings indicate that BOGR loaded composite films could be used as an active material for food packaging applications. [ABSTRACT FROM AUTHOR]

In this paper, we have examined eight new first‐row transition metal complexes (1–8). Mutli‐donor ligands based on barbituric and thiobarbituric acids were used in complexation reactions. The synthesized complexes were analyzed using FT‐IR and UV–vis spectroscopy, elemental (CHN) analysis, and single‐crystal X‐ray diffraction analysis. These complexes exhibited significant urease enzyme inhibition with IC50 values in the range of 13.73 ± 1.08–43.21 ± 1.50 μM. We observed excellent binding orientation of these complexes in the active site of Urease. The molecular docking results correlate well with in vitro observations. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a persistent, inflammatory skin condition that impacts approximately 15 to 20% of children and 1 to 3% of adults globally. Common skin manifestations include papules, papulovesicular, and brown or red patches with swelling, crusting, and flaking. Therefore, the drug abrocitinib (ABR) was approved by the US FDA as an oral treatment for atopic dermatitis. The present study outlines the development of innovative, thermostable, and pH‐stable organic solvent‐free nitrogen‐doped carbon dots (N@CQDs) synthesized through a one‐step method for evaluating ABR with a notable quantum yield of 33.84% to minimize the use of organic solvents. Their cost‐effectiveness, eco‐friendly characteristics, and outstanding photocatalytic properties have established them as a promising alternative to conventional luminescent techniques like fluorescent dyes and luminous derivatization technique. The reaction of ABR with N@CQDs led to a significant decrease in the luminescent response of the produced green and stable carbon quantum dots at 513 nm. The detection range was determined to be 1.0–150.0 ng mL−1, with a lower limit of quantitation (LOQ) equal to 0.52 ng mL−1 based on the linear graph. The green method effectively used for analysis of ABR in pharmaceutical tablets and pharmacokinetic study with high sensitivity. [ABSTRACT FROM AUTHOR]

In the present work, pectin and gelatin-based edible films (EFs) loaded with Citrus reticulata L. (tangerine) essential oil were fabricated and evaluated for their potential application in food packaging. GC–MS analysis and physiochemical, mechanical, and antioxidant analysis of the synthesized edible films and oil extract were carried out. GC–MS analysis of the tangerine essential oil revealed the presence of around 40 different chemical constituents, and among them, limonene (43.85%), linalyl acetate (19.16%), linalool (18.38%), and beta-Myrcene (3.41%) were found as the major constituent. Fourier transform infrared spectroscopy showed the interaction between the functional groups of the film components. Mechanical parameter assessment showed that the tensile strength of the edible film increases and elongation at break values decreases with oil addition. The thickness of the EFs increased with oil addition, while water solubility, water vapor permeability, and transparency decreased. In antioxidant potential assessment assays, maximum activity (DPPH• and ABTS•+ reducing potential) was reported for edible film samples containing a maximum amount (60 μL) of tangerine oil. We found that pectin and gelatin-based edible films loaded with tangerine essential oil exhibit better characteristics and could be used as a food packaging material. Practical Applications This study presents a potentially effective method for producing edible films using pectin and gelatin composite, that have been incorporated with tangerine essential oil. These films demonstrate superior properties and may serve as an effective choice for food packaging material. [ABSTRACT FROM AUTHOR]

Summary: This research focuses on the development and assessment of films composed of gelatin (GE) and calcium caseinate (CC), loaded with varying concentrations of petitgrain essential oil (PEO). A comprehensive assessment of the resulting films was conducted with a focus on the antioxidant, antibacterial, and physicochemical attributes. GCMS analysis identified the primary constituents of PEO, including linalyl acetate, linalool, α‐pinene, α‐terpineol, limonene, β‐myrcene, geranyl acetate, and neryl acetate. The antioxidant capacity of GE‐CC films increased significantly with increasing PEO concentration, as evidenced by DPPH and ABTS assays. Simultaneously, increased PEO concentration led to increased thickness, water vapour permeability (WVP), elongation at break (EAB), and water solubility (WS) in the active films while reducing moisture content (MC) and tensile strength (TS). In terms of optical characteristics, the transparency of the films decreased, while the b* (yellowness) and ΔE (total colour variation) values increased upon oil incorporation. The presence of intermolecular interactions between the polymers and the oil was confirmed through FTIR and morphological characteristics studied by SEM. The addition of PEO to the films resulted in improved thermal resistance against degradation, as observed in the thermo‐gravimetric analysis (TGA). Moreover, these active films showed potent antimicrobial activity against C. albicans and P. aeruginosa. In summary, this study underscores the suitability of GE‐CC films containing PEO for food packaging purposes, highlighting their functional characteristics and environmentally friendly nature. [ABSTRACT FROM AUTHOR]

A new method utilizing base catalysis is outlined for the synthesis of 1,4‐benzodioxepines, introducing a unique scaffold containing a seven‐membered ring heterocycle. The reaction proceeded under thermal conditions, with no waste was generated during the transformation, highlighting its remarkable atom efficiency and environmental friendliness. A straightforward metal‐free reaction condition utilizing 2‐propynyloxy benzyl alcohols as starting material and a catalytic amount of t‐BuOK in mesitylene at 100 °C for 1 hour was employed for this intramolecular cyclization transformation, resulting in the formation of 1,4‐Benzodioxepines in good to excellent yields and high regio‐ and diastereo‐selectivity. The density functional theory (DFT) calculations yielded the relative internal energy (U), enthalpy (H), and Gibbs free energy (G) values for all possible products, aligning closely with our experimental data. [ABSTRACT FROM AUTHOR]

Boswellia sacra and its derivatives exhibit notable bioactive properties, which have been the subject of extensive scientific research; however, their potential applications in food packaging remain largely untapped. In the current study, cellulose, sodium alginate, and gelatin composite edible films were fabricated with the addition of different concentrations (0.2% and 0.3%) of the ethanolic fraction of Boswellia sacra oleo gum resin (BSOR). The resultant films were examined for their physical, chemical, mechanical, barrier, optical, and antioxidant properties. Moreover, the films were characterized using Scanning Electron Microscopy (SEM), X‐ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) to study the impact of incorporating BSOR on the morphological, crystalline, and chemical properties of the films. The addition of BSOR increased the film thickness (0.026–0.08 mm), water vapor permeability (0.210–0.619 (g.mm)/(m2.h.kPa), and the intensity of the yellow color (3.01–7.20) while reducing the values of both tensile strength (6.67–1.03 MPa) and elongation at break (83.50%–48.81%). SEM and FTIR analysis confirmed the interaction between the BSOR and film‐forming components. The antioxidant properties of the edible films were significantly increased with the addition of BSOR. The comprehensive findings of the study demonstrated that BSOR possesses the potential to serve as an efficient natural antioxidant agent in the fabrication of edible films. [ABSTRACT FROM AUTHOR]

Three one‐pot reactions leading to six new transition metal complexes are presented. The one‐pot reactions involved transformations of 2‐(N'‐dicyanomethylene‐hydrazino)‐benzoic acid (DHB) into three new ligands (Lig‐I)2−, (Lig‐II)2−, and (Lig‐III)2−. The complex [Ni2(Lig‐I)2] ⋅ 3H2O (1) was prepared in a one‐pot synthesis in which ligand, (Lig‐I)2− was formed by the amination of DHB resulting from the nucleophilic attack of an amino group of ethylenediamine (en). The complex [Cu(Lig‐II)(en)(H2O)] (2) was prepared in a one‐pot synthesis in which ligand, (Lig‐II)2− was formed by the nucleophilic attack of an amino group of en resulting in an imidazole ring formation. The dinunclear complexes [Zn2(Lig‐III)2(CH3OH)2] (3) and [Cu2(Lig‐III)2(CH3OH)2] (4), a linear trinuclear complex [Ni3(Lig‐III)(en)2(CH3OH)] (5), and a mononuclear complex [Mn(Lig‐III)(CH3OH)4] (6) were synthesized using a preparation involving conversion of one of the nitriles on DHB into an imino‐ester. The resulting complexes were characterized using a variety of analytical techniques including infra‐red and UV‐vis spectroscopy, elemental analysis, and single‐crystal X‐ray diffraction analysis. The complexes displayed α‐glucosidase enzyme inhibition with IC50 values in the range of 1.57–207 μM. [ABSTRACT FROM AUTHOR]

The pharmaceutical sector has made considerable strides recently, emphasizing improving drug delivery methods to increase the bioavailability of various drugs. When used as a medication delivery method, nanoemulsions have multiple benefits. Their small droplet size, which is generally between 20 and 200 nanometers, creates a significant interfacial area for drug dissolution, improving the solubility and bioavailability of drugs that are weakly water-soluble. Additionally, nanoemulsions are a flexible platform for drug administration across various therapeutic areas since they can encapsulate hydrophilic and hydrophobic medicines. Nanoemulsion can be formulated in multiple dosage forms, for example, gels, creams, foams, aerosols, and sprays by using low-cost standard operative processes and also be taken orally, topically, topically, intravenously, intrapulmonary, intranasally, and intraocularly. The article explores nanoemulsion formulation and production methods, emphasizing the role of surfactants and cosurfactants in creating stable formulations. In order to customize nanoemulsions to particular medication delivery requirements, the choice of components and production techniques is crucial in assuring the stability and efficacy of the finished product. Nanoemulsions are a cutting-edge technology with a lot of potential for improving medication bioavailability in a variety of therapeutic contexts. They are a useful tool in the creation of innovative pharmaceutical formulations due to their capacity to enhance drug solubility, stability, and delivery. Nanoemulsions are positioned to play a crucial role in boosting medication delivery and enhancing patient outcomes as this field of study continues to advance. [ABSTRACT FROM AUTHOR]

Summary: This research was conducted in order to develop a sustainable and eco‐friendly pectin–sodium alginate‐based packaging material using natural additives. Cassia essential oil (CEO) is a GRAS‐approved natural preservative and flavouring agent used for a variety of food products. Recent reports revealed the growing interest in using oils in packaging material as natural additives. In the current study, CEO is loaded in pectin–sodium alginate‐based composite films. The main component observed in CEO was cinnamaldehyde which was evaluated by employing gas chromatography–mass spectrometry (GCMS) analysis. Moreover, the incorporation of CEO improved the tensile strength (TS) and elongation at break (EAB) and increased the opacity of the films. However, a decrease in the moisture content, water solubility and water vapour permeability was observed with the incorporation of EO. Additionally, SEM analysis of the CEO‐loaded films revealed an improvement in their morphology. The results of the DPPH and ABTS cation scavenging assays revealed a significant (P ≤ 0.05) increase in antioxidant activity with the incorporation of CEO. These findings indicate that cassia essential oil can be employed as a natural additive to develop edible active packaging material. [ABSTRACT FROM AUTHOR]

This study reports a mild reaction‐condition approach for the direct C−C bond cleavage of amides to form hydantoin structures in the presence of 4‐methylpyridine and a base. This approach presents an amide C−C bond cleavage strategy enabling nucleophilic addition to the amide carbonyl involving a reactive spiro intermediate. A broad spectrum of pseudo peptide Ugi adducts as bifunctional starting materials was synthesized and used in this transformation. The mechanistic pathway of this reaction was investigated using experimental and theoretical studies. [ABSTRACT FROM AUTHOR]

Inhibiting α‐glucosidase is a reliable method for reducing blood sugar levels in diabetic individuals. Several novel chromen‐linked hydrazine carbothioamide (3a–r) were designed and synthesized by condensation of chromone‐3‐carbaldehyde with a variety of substituted thiosemicarbazides. The structures of these new analogues were elucidated through various advanced spectroscopic techniques (1H NMR, 13C NMR, and ESI‐MS). The resulted compounds were screened for α‐glucosidase inhibitory potential and all the compounds (3a–r) exhibited potent inhibition of α‐glucosidase with IC50 values ranging 0.29–53.70 µM. Among them compounds 3c, 3f, 3h, and 3r displayed the highest α‐glucosidase inhibitor capability with IC50 values of 1.50, 1.28, 1.08, and 0.29 µM, respectively. Structure–activity relationship showed that different substituted groups are responsible for the variation in the α‐glucosidase inhibition. The kinetics studies of the most active inhibitor (3r) were performed, to investigate the mode of inhibition and dissociation constants (Ki), that indicated a competitive inhibitor with Ki value of 1.47 ± 0.31 µM. Furthermore, molecular docking studies was performed to reveal the possible interactions, such as H‐bonding, or π–π stacking, with the key residues of α‐glucosidase. Docking analysis revealed the importance of hydrazine carbothioamide moiety of compounds in the attachment of ligands with the crucial residues of α‐glucosidase. The estimated pharmacokinetic, physicochemical, and drug likeness properties of compounds 3a–r reflects that these molecules have acceptable range of these properties. [ABSTRACT FROM AUTHOR]

In the current era, the development of robust, eco‐friendly, and highly efficient electrocatalysts for generating hydrogen energy by water electrolysis has become a major challenge. This work explains the electrocatalytic performance of cost‐effective and amiable novel Ni‐BTC‐MWCNTs‐a as an active and effective electrocatalyst for OER in alkaline media. The catalytic activity of the nanocomposite is increased by heat treatment at 400°C temperature for 3 h. Systematic morphological and structural characterization studies of solvothermal synthesized materials were carried out by X‐ray powder diffraction (XRD) analysis, Fourier transform infrared (FTIR) spectroscopy technique, scanning electron microscopy (SEM) analysis, and energy dispersive X‐ray spectroscopy (EDS) analysis techniques. Metal–organic framework (MOF)‐based composites exhibit improved catalytic performance owing to the synergistic effect of Nickel BTC MOF, MWCNTs support, and high‐temperature annealing (400°C). Among all as‐synthesized materials, the annealed Ni‐BTC‐MWCNT‐a exhibits admirable catalytic performance for oxygen evolution reaction (OER) at low value for over potential (η) 243 m V, small Tafel slope value 57 mV dec−1, smaller charge transfer resistance (0.274 Ω), and higher electrochemical active surface area (2000 cm2) with maximum durability for 23 h and utilized as auspicious alternate with excellent catalytic activity in water splitting OER process for producing hydrogen energy at large scale other than highly expensive electrocatalysts of Ir, Ru, Pd, and Pt oxides. [ABSTRACT FROM AUTHOR]

Background/Aim: The knowledge of standardized care guidelines is critical to the confidence of practitioners in managing dental trauma. Therefore, the aim of this study was to assess the awareness, use and impact of the International Association of Dental Traumatology guidelines, and the online Dental Trauma Guide on general dental practitioners' self‐reported confidence and knowledge in managing traumatic dental injuries in the primary and permanent dentitions. Materials and Methods: A cross‐sectional, pre‐piloted, 27‐item self‐administered questionnaire survey was distributed electronically to general dental practitioners' working within five member states of the Gulf Cooperation Council countries (Kingdom of Bahrain, Kingdom of Saudi Arabia, Kuwait, Oman, and Qatar) between September and December 2020. Data were collected and analysed using descriptive statistics and Wilcoxon Signed Rank test analysis for relevant comparisons. Results: A total of 294 respondents completed the survey, with the majority being from the Kingdom of Saudi Arabia (47.4%) and Qatar (27.3%). A lack of evidence‐based knowledge in managing traumatic dental injuries was evident among more than half of the respondents. Respondents who were cognizant of the recent International Association of Dental Traumatology guidelines (2020) and those who use the Dental Trauma Guide routinely demonstrated a higher self‐reported confidence level in managing both simple and complex primary dentition trauma, as well as simple traumatic dental injuries in the permanent dentition (p <.05). Conclusion: This survey highlights critical deficiencies in the knowledge of a large number of the respondents in the management of dental trauma which is likely to cause irreversible long‐term patient effects. [ABSTRACT FROM AUTHOR]

The recent study was designed to explore Dodonaea viscosa, Juniperus excelsa, Helianthemum lippii, and Euryops pinifolius using methanolic (MeOH) extract. Their subfractions were examined against urease, carbonic anhydrase II (CA-II), α-glucosidase enzymes, and free radicals scavenging significance based on local practices via standard methods. Significance potential against the urease enzyme was presented by ethyl acetate fraction (EtOAc) of D. viscosa with (I C 50 = 125 ± 1.75 μg/mL), whereas the H. lippii (I C 50 = 1 46 ± 1.39 μg/mL) in the EtOAc was found efficient to scavenge the free radicals. Besides, that appreciable capacity was observed by the J. excelsa, D. viscosa, J. excelsa, and E. pinifolius as compared to the standard acarbose (I C 50 = 377.24 ± 1.14 μg/mL). Maximum significance was noticed in methanolic (MeOH) extract of J. excelsa and presented carbonic anhydrase CA-II (I C 50 = 5.1 ± 0.20 μg/mL) inhibition as compared to the standard (acetazolamide). We are reporting, for the first time, the CA-II inhibition of all the selected medicinal plants and α-glucosidase, urease, and antioxidant activities of the E. pinifolius. Thus, further screening is needed to isolate the promising bioactive ingredients which act as an alternative remedy to scavenge the free radicals, antiulcer, and act as a potential source to develop new antidiabetic drugs for controlling postprandial blood sugar as well as carbonic anhydrase inhibitors. [ABSTRACT FROM AUTHOR]

Long QT syndrome type II (LQT2) is caused by loss‐of‐function mutations in the hERG K+ channel, leading to increased incidence of cardiac arrest and sudden death. Many genetic variants have been reported in the hERG gene with various consequences on channel expression, permeation, and gating. Only a small number of LQT2 causing variants has been characterized to define the underlying pathophysiological causes of the disease. We sought to determine the characteristics of the frameshift variant p.Thr1019ProfsX38 (T1019PfsX38) which affects the C‐terminus of the protein. This mutation was identified in an extended Omani family of LQT2. It replaces the last 140 amino acids of hERG with 37 unique amino acids. T1019 is positioned at a distinguished region of the C‐terminal tail of hERG, as predicted from the deep learning system AlphaFold v2.0. We employed the whole‐cell configuration of the patch‐clamp technique to study wild‐type and mutant channels that were transiently expressed in human embryonic kidney 293 (HEK293) cells. Depolarizing voltages elicited slowly deactivating tail currents that appeared upon repolarization of cells that express either wild‐type‐ or T1019PfsX38‐hERG. There were no differences in the voltage and time dependencies of activation between the two variants. However, the rates of hERG channel deactivation at hyperpolarizing potentials were accelerated by T1019PfsX38. In addition, the voltage dependence of inactivation of T1019PfsX38‐hERG was shifted by 20 mV in the negative direction when compared with wild‐type hERG. The rates of channel inactivation were increased in the mutant channel variant. Next, we employed a step‐ramp protocol to mimic membrane repolarization by the cardiac action potential. The amplitudes of outward currents and their integrals were reduced in the mutant variant when compared with the wild‐type variant during repolarization. Thus, changes in the gating dynamics of hERG by the T1019PfsX38 variant contribute to the pathology seen in affected LQT2 patients. [ABSTRACT FROM AUTHOR]

A series of N‐((4‐sulfamoylphenyl)carbamothioyl)alkanamides (5a‐j) were synthesized by the reaction of sulphanilamide in dry acetone with freshly prepared alkyl and acyl isothiocyanates (5a‐j). The structures of products were confirmed by IR, 1H, and 13C NMR. The synthesized compounds were screened as inhibitors of the bovine erythrocyte carbonic anhydrase isoform II (bCA II) and 15‐lipoxygenase enzyme (15‐LOX). Most of the derivatives showed significant activity against bCA‐II while only few compounds were found active against 15‐LOX. Molecular docking studies of most active compounds were carried out against bCA II as well as 15‐LOX to rationalize the binding mode and interactions of compound in the active sites. Additionally, the pharmacokinetic properties of the compounds were predicted through computational tools, which reflect that these compounds possess acceptable pharmacokinetic profile and good drug‐likeness. [ABSTRACT FROM AUTHOR]

In the current study, a series of stabilized bis‐acetylene incorporated 4‐hydroxybenzaldehyde based macrocycles using the alkyne‐homocoupling approach were synthesized in moderate yields. A total of six newly stiff macrocycles were synthesized in a stepwise manner starting from 4‐hydroxybenzaldehyde. In the first step, base mediated propargylation was performed followed by copper mediated terminal alkyne homocoupling. The alkyne homocoupled substrate having carbonyl at both the terminals is cyclized in the final step via double imine formation reactions using substituted diamines as linker. All the newly synthesized rigid framework of the macrocycles were optimized at B3LYP/6‐31G (d,p) level of theory. Nonlinear optical behaviors of the synthesized macrocycles were explored by the DFT calculations where high values of first‐order hyperpolarizability and dipole moment were examined. In the reported study, a good agreement between experimental and theoretical parameters was observed that may play a significant contribution for the NLO applications. [ABSTRACT FROM AUTHOR]

In search for α‐glucosidase inhibitors used in the treatment of diabetes mellitus, a series of unique benzimidazole based hydrazones derivatives were synthesized (5a‐5p), which were then investigated for their in vitro α‐glucosidase inhibitory potential. The compounds of interest were characterized by modern spectroscopic approaches including CHN, 1HNM R, 13CN MR and FTIR. The structure of compound 5n was distinctively authenticated through single crystal X‐ray study. All compounds depicted potent enzyme inhibitory potential with IC50 values in the range of 2.25 ± 0.01 to 81.16 ± 0.12 μM except 5n that showed IC50 value of 182.75 ± 0.13 μM. A limited structure–activity correlation demonstrated that substitutions of isatin, aldehydes and ketone in hydrazones moiety had remarkable contribution in the overall activity and that was further supported by molecular docking studies carried out in elucidating the mechanism of binding interaction of these compounds in the catalytic site of α‐glucosidase. [ABSTRACT FROM AUTHOR]

Endothelin is a chemical mediator that helps in maintaining balance within the blood-brain barrier by regulating the levels of toxicants and molecules which pass through the brain, suggesting that a rise in its production determines Alzheimer's disease. The inequity in the amyloid β occurs due to a problem in its clearance from the brain initiating the production of reactive oxygen species and superoxide that activates a cascade wherein the release of inflammatory mediators and various enzymes like endothelin-converting enzymes take place. Furthermore, the cascade increases the levels of endothelin in the brain from endothelial cells. Endothelin levels are upregulated, which can be regulated by modulating the action of endothelin-converting enzymes and endothelin receptors. Hence, endothelin paves a pathway in the treatment of Alzheimer's disease. In this article, we have covered various mechanisms and preclinical studies that support and direct endothelin involvement in the progression of Alzheimer's disease by using various search tools such as PubMed, Science Direct, and Medline. Conclusive outcome data were extracted that all together defy contrivance pathways, potential drugs, endothelin receptors, and endothelin enzymes in our article giving profound importance to target endothelin for prevention and treatment of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

In times of health crisis, including the current COVID‐19 pandemic, the potential benefit of botanical drugs and supplements emerges as a focus of attention, although controversial efficacy claims are rightly a concern. Phytotherapy has an established role in everyday self‐care and health care, but, since botanical preparations contain many chemical constituents rather than single compounds, challenges arise in demonstrating efficacy and safety. However, there is ample traditional, empirical, and clinical evidence that botanicals can offer some protection and alleviation of disease symptoms as well as promoting general well‐being. Newly emerging viral infections, specifically COVID‐19, represent a unique challenge in their novelty and absence of established antiviral treatment or immunization. We discuss here the roles and limitations of phytotherapy in helping to prevent and address viral infections, especially regarding their effects on immune response. Botanicals with a documented immunomodulatory, immunostimulatory, and antiinflammatory effects include adaptogens, Boswellia spp., Curcuma longa, Echinacea spp., Glycyrrhiza spp., medicinal fungi, Pelargonium sidoides, salicylate‐yielding herbs, and Sambucus spp. We further provide a clinical perspective on applications and safety of these herbs in prevention, onset, progression, and convalescence from respiratory viral infections. [ABSTRACT FROM AUTHOR]

An artificial series of macrocycles based on 4,4′‐sulfonyldiphenol intermediate was synthesized using a multistep procedure involving oxidation of bisphenol sulfide, etherification of phenolic hydroxyl groups, and final ring closure with different diamines. Different chemical species having aromatic, heteroaromatic, and aliphatic characters were incorporated into macrocyclic frameworks in the final step of ring closure. This simple and easily executable synthetic strategy was applied to synthesize 15 macrocycles (5a‐o) in excellent yields. Characterization of the synthesized products was achieved through well‐known modern spectroscopic techniques such as IR, NMR, and Mass. Macrocycles 5m and 5n were found to show significant AChE inhibition with IC50 values of 76.9 ± 0.24 and 71.2 ± 0.77 μM, respectively. Macrocycle 5n was also found to be an active inhibitor of butyrylcholinesterase (BChE) with IC50 score of 55.3 ± 0.54 μM. Among others, macrocycle 5l cyclized with o‐phenylenediamine demonstrated moderate inhibition with IC50 value of 81.1 ± 0.54 μM. Increasing interest in studying interactions of macrocycles with different enzymatic targets compelled us to design and synthesize sulfone‐based macrocycles that might prove as highly potent class of biologically active compounds. [ABSTRACT FROM AUTHOR]

A series of new heterocycles (4–18) was synthesized by the structural modification of benzimidazole‐2‐thiol (BT, 2‐MBI). The structures of the synthesized compounds were confirmed with the help of high‐resolution mass spectrometry (HRMS) and 1HNMR spectroscopy. High inhibitions of the oxidants such as ABTS and DPPH were observed for compounds 9 [IC50(s) = 167.4 μM (ABTS), 139.5 μM (DPPH)], 10 [IC50(s) = 186.5 μM (ABTS), 155.4 μM (DPPH)], 11 [IC50(s) = 286.1 μM (ABTS), 189.1 μM (DPPH)], 12 [IC50(s) = 310.8 μM (ABTS), 162.2 μM (DPPH)], 14 [IC50(s) = 281.3 μM (ABTS), 205.7 μM (DPPH)], 15 [IC50(s) = 284.1 μM (ABTS), 177.3 μM (DPPH)], and 16 [IC50(s) = 344.7 μM (ABTS), 270.2 μM (DPPH)] as compared with Ascorbic acid [IC50(s) = 340.9 μM (ABTS), 164.3 μM (DPPH)]. The anti‐Alzheimer's activity was performed in vitro against cholinesterase enzymes (AChE, BChE). Compound 11 was able to show significant inhibitions [IC50(s) = 121.2 μM (AChE), 38.3 μM (BChE)] as against that of galantamine [IC50(s) = 139.4 μM (AChE), 40.3 μM (BChE)]. Compound 14 was found as a very good inhibitor of butyrylcholinesterase (IC50 = 35.4 μM) as compared with standard galantamine. Molecular docking was further performed to investigate the mechanism of anticholinesterase activity. [ABSTRACT FROM AUTHOR]

Various synthesized Pillar[5]arene macrocycles were allowed to form complexes with the ionic liquid; 1‐Butyl‐3‐methyl‐imidazolium tetrafluoroborate (IL). The pillar[5]arenes used in the study were synthesized by the established pioneering method of Ogoshi that involves treatment of 1,4‐disubstituted benzenes with paraformaldehyde in the presence of BF3.OEt2. Selected synthesized pillar[5]arenes; DMpillar[5]arene (4a), DPpillar[5]arene (4b), DPGpillar[5]arene (4c) were allowed to form complexes with the ionic liquid, and complexations were confirmed by MALDI‐TOF, ESI‐MS, 1H NMR, and DOSY spectroscopy. ESI‐MS reveals highly intense ion peaks that correspond to [pillar[5]arene+IL]+ for the complexes of the three pillar[5]arenes with the ionic liquid. Changes in characteristic peaks in hosts and guests, as a result of complexation, were studied by 1H NMR. Results obtained suggest a formation of 1 : 1 complexes between the pillar[5]arene host and the IL guest. Host‐guest interactions in such complexes have also been studied using 1H‐1H 2D ROESY NMR spectroscopy. Obtained through‐space correlations revealed interactions between certain parts of the pillar[5]arene hosts and the ionic liquid. The complexation between the three pillar[5]arenes and the IL was studied by molecular dynamics (MD) simulations. The obtained results suggest the insertion of the IL inside the nanocavities of the hosts. [ABSTRACT FROM AUTHOR]

Introduction: We investigated the frequency, neuropathology, and phenotypic characteristics of spastic paraplegia (SP) that precedes dementia in presenilin 1 (PSEN1) related familial Alzheimer's disease (AD). Methods: We performed whole exome sequencing (WES) in 60 probands with hereditary spastic paraplegia (HSP) phenotype that was negative for variants in known HSP‐related genes. Where PSEN1 mutation was identified, brain biopsy was performed. We investigated the link between HSP and AD with PSEN1 in silico pathway analysis and measured in vivo the stability of PSEN1 mutant γ‐secretase. Results: We identified a PSEN1 variant (p.Thr291Pro) in an individual presenting with pure SP at 30 years of age. Three years later, SP was associated with severe, fast cognitive decline and amyloid deposition with diffuse cortical plaques on brain biopsy. Biochemical analysis of p.Thr291Pro PSEN1 revealed that although the mutation does not alter active γ‐secretase reconstitution, it destabilizes γ‐secretase‐amyloid precursor protein (APP)/amyloid beta (Aβn) interactions during proteolysis, enhancing the production of longer Aβ peptides. We then extended our analysis to all 226 PSEN1 pathogenic variants reported and show that 7.5% were associated with pure SP onset followed by cognitive decline later in the disease. We found that PSEN1 cases manifesting initially as SP have a later age of onset, are associated with mutations located beyond codon 200, and showed larger diffuse, cored plaques, amyloid‐ring arteries, and severe CAA. Discussion: We show that pure SP can precede dementia onset in PSEN1‐related familial AD. We recommend PSEN1 genetic testing in patients presenting with SP with no variants in known HSP‐related genes, particularly when associated with a family history of cognitive decline. [ABSTRACT FROM AUTHOR]

Urea is added as an adulterant to give milk whiteness and increase its consistency for improving the solid not fat percentage, but the excessive amount of urea in milk causes overburden and kidney damages. Here, an innovative sensitive methodology based on near‐infrared spectroscopy coupled with multivariate analysis has been proposed for the robust detection and quantification of urea adulteration in fresh milk samples. In this study, 162 fresh milk samples were used, those consisting 20 nonadulterated samples (without urea) and 142 with urea adulterant. Eight different percentage levels of urea adulterant, that is, 0.10%, 0.30%, 0.50%, 0.70%, 0.90%, 1.10%, 1.30%, and 1.70%, were prepared, each of them prepared in triplicates. A Frontier NIR spectrophotometer (BSEN60825‐1:2007) by Perkin Elmer was used for scanning the absorption of each sample in the wavenumber range of 10,000–4,000 cm‐1, using 0.2 mm path length CaF2 sealed cell at resolution of 2 cm‐1. Principal components analysis (PCA), partial least‐squares discriminant analysis (PLS‐DA), and partial least‐squares regressions (PLSR) methods were applied for the multivariate analysis of the NIR spectral data collected. PCA was used to reduce the dimensionality of the spectral data and to explore the similarities and differences among the fresh milk samples and the adulterated ones. PLS‐DA also showed the discrimination between the nonadulterated and adulterated milk samples. The R‐square and root mean square error (RMSE) values obtained for the PLS‐DA model were 0.9680 and 0.08%, respectively. Furthermore, PLSR model was also built using the training set of NIR spectral data to make a regression model. For this PLSR model, leave‐one‐out cross‐validation procedure was used as an internal cross‐validation criteria and the R‐square and the root mean square error (RMSE) values for the PLSR model were found as 0.9800 and 0.56%, respectively. The PLSR model was then externally validated using a test set. The root means square error of prediction (RMSEP) obtained was 0.48%. The present proposed study was intended to contribute toward the development of a robust, sensitive, and reproducible method to detect and determine the urea adulterant concentration in fresh milk samples. [ABSTRACT FROM AUTHOR]

The coordination chemistry of 1,10‐phenanthroline (phen) and sodium 1,3‐benzothiazole‐2‐thiolate (SBT) with selected s‐block elements has been investigated. Four metal complexes were prepared and their structures were characterized using a variety of analytical techniques including infrared, UV–visible, 1H NMR and 13C NMR spectroscopies, elemental analysis, mass spectrometry and single‐crystal X‐ray diffraction. The reactions of phen and SBT with M(X)n (M = K(I), Cs(I), Mg(II), Sr(II); X = OH−, CO3−, Cl−; n = 1, 2) in MeOH–H2O yielded one‐dimensional chains of both potassium [K2(phen)2(BT)2(H2O)4]n (1) and caesium [Cs(phen)(BS)(H2O)]n (2) (where BT = 1,3‐benzthiazole‐2‐thiolate and BS = 1,3‐benzthiazole‐2‐sulfinothiolate) and mononuclear complexes of both magnesium {[Mg(phen)(H2O)4](BT)2·phen} (3) and strontium {[Sr(phen)2(H2O)4](BT)2} (4). In these complexes, phen binds via an N,N′ chelate pocket, while the monoanonic BT− ligands either coordinate in a bidentate fashion (in the case of 1) or remain uncoordinated (in the case of 3 and 4). In complex 2, SBT ligand was oxidized in situ into a new BS ligand. The sulfinothiolate oxygen atoms in BS coordinate with caesium in a tridentate fashion. Complexes 1–4 were evaluated against urease for enzyme inhibition. The complexes displayed significant inhibition with IC50 values in the range 10.8–45.8 μM. In order to examine the structure–activity relationship, the complexes were docked at the active site of urease. Docking results clearly demonstrate the binding of each complex within the active site of the enzyme. [ABSTRACT FROM AUTHOR]

An aminopyridinium ionic liquid is presented as a green, tunable, and active metal-free one-component catalytic system for the atom-efficient transformation of oxiranes and CO2 to cyclic carbonates. Inclusion of a positively charged moiety into aminopyridines, through a simple single-step synthesis, provides a one-component ionic liquid catalytic system with superior activity; effective in ring opening of epoxide, CO2 inclusion, and stabilization of oxoanionic intermediates. An efficiency assessment of a variety of positively charged aminopyridines was pursued, and the impact of temperature, catalyst loading, and the kind of nucleophile on the catalytic performance was also investigated. Under solvent-free conditions, this bifunctional organocatalytic system was used for the preparation of 18 examples of cyclic carbonates from a broad range of alkyl- and aryl-substituted oxiranes and CO2, where up to 98% yield and high selectivity were achieved. DFT calculations validated a mechanism in which nucleophilic ring-opening and CO2 inclusion occur simultaneously towards cyclic carbonate formation. [ABSTRACT FROM AUTHOR]

To overcome the biofouling challenge which faces membrane water treatment processed, the novel superhydrophobic carbon nanomaterials impregnated on/powder activated carbon (CNMs/PAC) was utilized to successfully design prepare an antimicrobial membrane. The research was conducted following a systematic statistical design of experiments technique considering various parameters of composite membrane fabrication. The impact of these parameters of composite membrane on Staphylococcus aureus growth was investigated. The bacteria growth was analyzed through spectrophotometer and SEM. The effect of CNMs' hydrophobicity on the bacterial colonies revealed a decrease in the abundance of bacterial colonies and an alteration in structure with increasing the hydrophobicity. The results revealed that the optimum preparative conditions for carbon loading CNMs/PAC was 363.04 mg with a polymer concentration of 22.64 g/100 g, and a casting knife thickness of 133.91 μm. These conditions have resulted in decreasing the number of bacteria colonies to about 7.56 CFU. Our results provided a strong evidence on the antibacterial effect and consequently on the antibiofouling potential of CNMs/PAC in membrane. [ABSTRACT FROM AUTHOR]

Reactions of 1,10‐phenanthroline (phen) and 2‐(3,4‐dichlorophenyl)acetic acid (dcaH) with Mn(CO3) (M = LiI, NaI and MgII; n = 1 and 2) in MeOH yield the mononuclear lithium complex aqua[2‐(3,4‐dichlorophenyl)acetato‐κO](1,10‐phenanthroline‐κ2N,N′)lithium(I), [Li(C8H5Cl2O2)(C12H8N2)(H2O)] or [Li(dca)(phen)(H2O)] (1), the dinuclear sodium complex di‐μ‐aqua‐bis{[2‐(3,4‐dichlorophenyl)acetato‐κO](1,10‐phenanthroline‐κ2N,N′)sodium(I)}, [Na2(C8H5Cl2O2)2(C12H8N2)2(H2O)2] or [Na2(dca)2(phen)2(H2O)2] (2), and the one‐dimensional chain magnesium complex catena‐poly[[[diaqua(1,10‐phenanthroline‐κ2N,N′)magnesium]‐μ‐2‐(3,4‐dichlorophenyl)acetato‐κ2O:O′] 2‐(3,4‐dichlorophenyl)acetate monohydrate], {[Mg(C8H5Cl2O2)(C12H8N2)(H2O)2](C8H5Cl2O2)·H2O}n or {[Mg(dca)(phen)(H2O)2](dca)·H2O}n (3). In these complexes, phen binds via an N,N′‐chelate pocket, while the deprotonated dca− ligands coordinate either in a monodentate (in 1 and 2) or bidentate (in 3) fashion. The remaining coordination sites around the metal ions are occupied by water molecules in all three complexes. Complex 1 crystallizes in the triclinic space group P with one molecule in the asymmetric unit. The Li+ ion adopts a four‐coordinated distorted seesaw geometry comprising an [N2O2] donor set. Complex 2 crystallizes in the triclinic space group P with half a molecule in the asymmetric unit, in which the Na+ ion adopts a five‐coordinated distorted spherical square‐pyramidal geometry, with an [N2O3] donor set. Complex 3 crystallizes in the orthorhombic space group P212121, with one Mg2+ ion, one phen ligand, two dca− ligands and three water molecules in the asymmetric unit. Both dcaH ligands are deprotonated, however, one dca− anion is not coordinated, whereas the second dca− anion coordinates in a bidentate fashion bridging two Mg2+ ions, resulting in a one‐dimensional chain structure for 3. The Mg2+ ion adopts a distorted octahedral geometry, with an [N2O4] donor set. Complexes 1–3 were evaluated against urease and α‐glucosidase enzymes for their inhibition potential and were found to be inactive. Reactions of 1,10‐phenanthroline (phen) and 2‐(3,4‐dichlorophenyl)acetic acid (dcaH) with Mn(CO3) (M = LiI, NaI and MgII; n = 1 and 2) in MeOH yield the mononuclear lithium complex, the dinuclear sodium complex and the one‐dimensional chain magnesium complex. In these complexes, phen binds via an N,N′‐chelate pocket, while the deprotonated dca− ligands coordinate either in a monodentate or bidentate fashion. [ABSTRACT FROM AUTHOR]

Squaramide–quaternary ammonium salt is illustrated as a simple, tunable, and competent metal‐free binary catalytic platform for the atom‐economic conversion of epoxides and isocyanates into oxazolidinones. Although, various metal catalysts have been employed for the title reaction, application of organocatalysis is scarce. At first, a rational survey of catalytic activity of several air‐stable and architecturally distinct squaramides was undertaken. Thereafter, the impact on catalytic capability of different parameters, such as temperature, catalyst loading, and nature of nucleophiles, was examined. This binary organocatalytic system for the oxazolidinone synthesis, composed of a squaramide entity along with a suitable halide anion, was applied to the challenging conversion of a plethora of alkyl‐ and aryl‐substituted epoxides– including disubstituted and enantioenriched ones– and isocyanates into the corresponding oxazolidinones in high‐to‐excellent yields. The time‐dependent formation of oxazolidinone from epoxide and isocyanate was monitored by FTIR‐ATR and 1H NMR spectroscopy and the scalability of this process was also described. In light of 1H NMR experiment, a hydrogen‐bonding/anion‐binding mechanism was proposed wherein the nucleophilic ring‐opening operation, and oxo‐ and carbamate‐anions stabilization occur cooperatively towards isocyanate fixation. [ABSTRACT FROM AUTHOR]

An electrostatically enhanced phenol as a simple and competent bifunctional organocatalyst for the atom‐economical conversion of epoxides to cyclic carbonates under environmentally benign conditions is described. Incorporating a positively charged center into phenols through a modular one‐step synthesis results in a bifunctional system with enhanced acidity and reactivity, capable of epoxide activation, a halide nucleophilic ring‐opening process, and CO2 incorporation in a synergistic fashion. A rational survey of the efficiency of different positively charged phenols and the influence of different parameters, such as temperature, catalyst loading, and the nature of the nucleophile, on catalytic activity was conducted. In addition, the time‐dependent conversion of epoxide into the corresponding cyclic carbonate was further explored by FTIR‐ATR and 1H NMR spectroscopy. This bifunctional catalytic platform is among one of the mildest and most efficient metal‐free systems that is capable of converting a variety of epoxides into cyclic carbonates under virtually ambient conditions. The 1H NMR titration experiment validated the bifunctional catalytic mechanism wherein both the epoxide activation and the nucleophilic ring‐opening process occur in concert en route to carbon dioxide fixation. All in one: An electrostatically enhanced phenol as a simple and competent bifunctional organocatalyst for the conversion of epoxides to cyclic carbonates under environmentally benign conditions is described. Incorporating a positively charged center into phenols results in a bifunctional system with enhanced acidity and reactivity, capable of epoxide activation, a halide nucleophilic ring‐opening process, and CO2 incorporation. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Incensole can be considered as a biomarker for Boswellia species which is a diterpene that has received remarkable pharmacological interest recently due to its potent anti‐inflammatory and anti‐depressant activity. Objective: Near‐infrared (NIR) spectroscopy coupled with PLSR (partial least squares regression) as a robust, rapid and alternative method was used to quantify the content of incensole in three species namely B. papyrifera, B. sacra and B. serrata and cross‐validated by high‐performance liquid chromatography (HPLC). Materials and Methods: NIR spectrophotometer was used for the quantification of incensole standards and Boswellia species in absorption mode in the wavelength range between 700 and 2500 nm. A PLSR model was built from the obtained spectral data using 70% of the incensole working standard solutions (training set), ranging from 0.5 to 100 ppm. The PLSR model obtained has a R2 value of 98% with a correlationship of 0.99 and a good prediction with root mean square error for prediction (RMSEP) value of 3.2%. Results: The results indicated that the methanol (MeOH) extract of B. papyrifera resin has the highest concentration of incensole (18.4%) followed by n‐hexane (13.5%) and ethyl acetate (3.6%) while trace amounts was detected in the fractions of B. sacra and no incensole was detected in the fractions of B. serrata. Conclusion: The findings are in total agreement with the HPLC analysis suggesting that NIR spectroscopy coupled with PLSR is a robust, rapid and non‐destructive alternate method for the quantification of incensole in B. papyrifera. Copyright © 2018 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Novel substituted amino acid tethered norsufentanil derivatives were synthesized by the four‐component Ugi reaction. Norsufentanil was reacted with succinic anhydride to produce the corresponding carboxylic acid. The resulting carboxylic acid has undergone a multicomponent reaction with different aldehydes, amines, and isocyanides to produce a library of the desired compounds. In all cases, amide bond rotation was observed in the NMR spectra. In vivo analgesic activity of the synthesized compounds was evaluated by a tail flick test. Very encouraging results were obtained for a number of the synthesized products. Some of the synthesized compounds such as 5a, 5b, 5h, 5j, and 5r were found to be more potent than sufentanil, sufentanil citrate, and norsufentanil. Binding modes between the compounds and mu and delta‐opioid receptors were studied by molecular docking method. The relationship between the molecular structural features and the analgesic activity was investigated by a quantitative structure–activity relationship model. The results of the molecular modeling studies and the in vivo analgesic activity suggested that the majority of the synthesized compounds were more potent than sufentanil and norsufentanil. [ABSTRACT FROM AUTHOR]