Stability-Indicating Densitometric High-Performance Thin-Layer Chromatographic Method for the Quantitative Analysis of Biomarker Naringin in the Leaves and Stems of Rumex vesicarius L.

JPC – Journal of Planar Chromatography – Modern TLC - A simple, sensitive, and stability-indicating high-performance thinlayer chromatography (HPTLC)-densitometric method was developed...     

Facile synthesis of unusual glycosyl carbamates and amino acid glycosides from propargyl 1,2-orthoesters as glycosyl donors

Propargyl 1,2-O-orthoesters are exploited for the synthesis of 1,2-trans O-glycosides of protected amino acids. N-Fmoc- and N-Cbz protected serine/threonine - benzyl/methyl esters reacted well with glucosyl-, galactosyl-, mannosyl- and lactosyl- derived propargyl 1,2-orthoesters affording respective 1,2-trans glycosides in good yields under AuBr(3)/4 ? MS Powder/CH(2)Cl(2)/rt. t-Boc serine derivative gave serine 1,2-orthoester and glycosyl carbamate. Optimized conditions enabled preparation of new glycosyl carbamates from N-Boc protected amines in a single step using gold catalysts and propargyl 1,2-orthoesters in excellent yields.     

Copper(II)-catalyzed conversion of bisaryloxime ethers to 2-arylbenzoxazoles via C-H functionalization/C-N/C-O bonds formation

A copper(II)-catalyzed conversion of bisaryloxime ethers to 2-arylbenzoxazoles has been developed. The reaction involves a cascade C-H functionalization and C-N/C-O bond formation under oxygen atmosphere.     

The Effects of Structural Alterations in the Polyamine and Amino Acid Moieties of Philanthotoxins on Nicotinic Acetylcholine Receptor Inhibition in the Locust,Schistocerca gregaria

Alterations in the polyamine and amino acid (tyrosine) moieties of philanthotoxin-343 (PhTX-343) were investigated for their effects on the antagonism of nicotinic acetylcholine receptors (nAChRs) isolated from the locust (Schistocerca gregaria) mushroom body. Through whole-cell patch-clamp recordings, the philanthotoxin analogues in this study were shown to cause inhibition of the inward current when co-applied with acetylcholine (ACh). PhTX-343 (IC₅₀ = 0.80 μM at −75 mV) antagonised locust nAChRs in a use-dependent manner, suggesting that it acts as an open-channel blocker. The analogue in which both the secondary amine functionalities were replaced with methylene groups (i.e., PhTX-12) was ~6-fold more potent (IC₅₀ (half-maximal inhibitory concentration) = 0.13 μM at −75 mV) than PhTX-343. The analogue containing cyclohexylalanine as a substitute for the tyrosine moiety of PhTX-343 (i.e., Cha-PhTX-343) was also more potent (IC₅₀ = 0.44 μM at −75 mV). A combination of both alterations to PhTX-343 generated the most potent analogue, i.e., Cha-PhTX-12 (IC₅₀ = 1.71 nM at −75 mV). Modulation by PhTX-343 and Cha-PhTX-343 fell into two distinct groups, indicating the presence of two pharmacologically distinct nAChR groups in the locust mushroom body. In the first group, all concentrations of PhTX-343 and Cha-PhTX-343 inhibited responses to ACh. In the second group, application of PhTX-343 or Cha-PhTX-343 at concentrations ≤100 nM caused potentiation, while concentrations ≥ 1 μM inhibited responses to ACh. Cha-PhTX-12 may have potential to be developed into insecticidal compounds with a novel mode of action.     

A mild and regioselective method for alpha-bromination of beta-keto esters and 1,3-diketones using bromodimethylsulfonium bromide (BDMS)

Bromodimethylsulfonium bromide has been found to be an effective and regioselective reagent for alpha-monobromination of beta-keto esters and 1,3-diketones. A wide variety of beta-keto esters and 1,3-diketones undergo chemoselective alpha-monobromination with excellent yields at 0-5 degrees C or room temperature. The notable advantages of this protocol are no need of chromatographic separation, use of less hazardous reagent than molecular bromine, and no added base, Lewis acid, or other catalyst.     

Concurrent Analysis of the Biologically Active Markers β-Amyrin and β-Sitosterol by Applying a Validated High-Performance Thin-Layer Chromatography Method in the Aerial Parts of Tinospora cordifolia and Calotropis gigantia

JPC – Journal of Planar Chromatography – Modern TLC - In this study, we have developed a validated high-performance thin-layer chromatography (HPTLC) method for the concurrent...     

Response Surface Methodology (RSM)-Based Optimization of Ultrasound-Assisted Extraction of Sennoside A,Sennoside B,Aloe-Emodin,Emodin, and Chrysophanol from Senna alexandrina (Aerial Parts): HPLC-UV and Antioxidant Analysis

In this study, ultrasound-assisted extraction conditions were optimized to maximize the yields of sennoside A, sennoside B, aloe-emodin, emodin, and chrysophanol from S. alexandrina (aerial parts). The three UAE factors, extraction temperature (S₁), extraction time (S₂), and liquid to solid ratio (S₃), were optimized using response surface methodology (RSM). A Box–Behnken design was used for experimental design and phytoconstituent analysis was performed using high-performance liquid chromatography-UV. The optimal extraction conditions were found to be a 64.2 °C extraction temperature, 52.1 min extraction time, and 25.2 mL/g liquid to solid ratio. The experimental values of sennoside A, sennoside B, aloe-emodin, emodin, and chrysophanol (2.237, 12.792, 2.457, 0.261, and 1.529%, respectively) agreed with those predicted (2.152, 12.031, 2.331, 0.214, and 1.411%, respectively) by RSM models, thus demonstrating the appropriateness of the model used and the accomplishment of RSM in optimizing the extraction conditions. Excellent antioxidant properties were exhibited by S. alexandrina methanol extract obtained using the optimized extraction conditions with a DPPH assay (IC50 = 59.7 ± 1.93, µg/mL) and ABTS method (47.2 ± 1.40, µg/mL) compared to standard ascorbic acid.     

Secondary metabolism of olive secoiridoids. New microcomponents detected in drupes by electrospray ionization and high-resolution tandem mass spectrometry

Olive drupe tissues have been selected as a possible source of information about the secondary metabolism of oleaceae secoiridoids. The structures of a number of new microcomponents, detected and isolated by a combined high-performance liquid chromatography (HPLC)-fraction collector/ultraviolet electrospray ionization mass spectrometry (UV/ESI-MS) apparatus, can be inferred from the data obtained by high-resolution tandem mass spectrometry in a QqTOF instrument. Some of them (1, 2, 3 and 4) are closely correlated to oleuropein. Others, such as neo-nuzhenide (5) and 2'-hydroxyoleuropein (6), typical of other oleaceae families, have never been found in olive tissues.     

Box–Behnken Design (BBD)-Based Optimization of Microwave-Assisted Extraction of Parthenolide from the Stems of Tarconanthus camphoratus and Cytotoxic Analysis

Parthenolide, a strong cytotoxic compound found in different parts of Tarchonanthus camphoratus which motivated the authors to develop an optimized microwave-assisted extraction (MEA) method using Box–Behnken design (BBD) for efficient extraction of parthenolide from the stem of T. camphoratus and its validation by high-performance thin-layer chromatography (HPTLC) and cytotoxic analysis. The optimized parameters for microwave extraction were determined as: 51.5 °C extraction temperature, 50.8 min extraction time, and 211 W microwave power. A quadratic polynomial model was found the most suitable model with R² of 0.9989 and coefficient of variation (CV) of 0.2898%. The high values of adjusted R² (0.9974), predicted R² (0.9945), and signal-to-noise ratio (74.23) indicated a good correlation and adequate signal, respectively. HPTLC analyzed the parthenolide (R_f = 0.16) content in T. camphoratus methanol extract (TCME) at λ_max = 575 nm and found it as 0.9273% ± 0.0487% w/w, which was a higher than expected yield (0.9157% w/w). The TCME exhibited good cytotoxicity against HepG2 and MCF-7 cell lines (IC₅₀ = 30.87 and 35.41 µg/mL, respectively), which further supported our findings of high parthenolide content in TCME. This optimized MAE method can be further applied to efficiently extract parthenolide from marketed herbal supplements containing different Tarconanthus species.     

Nek2 Kinase Signaling in Malaria,Bone, Immune and Kidney Disorders to Metastatic Cancers and Drug Resistance: Progress on Nek2 Inhibitor Development

Cell cycle kinases represent an important component of the cell machinery that controls signal transduction involved in cell proliferation, growth, and differentiation. Nek2 is a mitotic Ser/Thr kinase that localizes predominantly to centrosomes and kinetochores and orchestrates centrosome disjunction and faithful chromosomal segregation. Its activity is tightly regulated during the cell cycle with the help of other kinases and phosphatases and via proteasomal degradation. Increased levels of Nek2 kinase can promote centrosome amplification (CA), mitotic defects, chromosome instability (CIN), tumor growth, and cancer metastasis. While it remains a highly attractive target for the development of anti-cancer therapeutics, several new roles of the Nek2 enzyme have recently emerged: these include drug resistance, bone, ciliopathies, immune and kidney diseases, and parasitic diseases such as malaria. Therefore, Nek2 is at the interface of multiple cellular processes and can influence numerous cellular signaling networks. Herein, we provide a critical overview of Nek2 kinase biology and discuss the signaling roles it plays in both normal and diseased human physiology. While the majority of research efforts over the last two decades have focused on the roles of Nek2 kinase in tumor development and cancer metastasis, the signaling mechanisms involving the key players associated with several other notable human diseases are highlighted here. We summarize the efforts made so far to develop Nek2 inhibitory small molecules, illustrate their action modalities, and provide our opinion on the future of Nek2-targeted therapeutics. It is anticipated that the functional inhibition of Nek2 kinase will be a key strategy going forward in drug development, with applications across multiple human diseases.