Comparison and Determination of the Content of Mosapride Citrate by Different qNMR Methods.

As a salt-type compound, mosapride citrate's metabolism and side effects are correlated with its salt-forming ratio. Several techniques were developed in this work to compare various quantitative nuclear magnetic resonance (qNMR) methodologies and to quantitatively examine the content of raw materials. Among the qNMR techniques, methods for H NMR and F NMR were developed.

Economical and rapid enantioselective, diastereoselective and achiral separation of palonosetron hydrochloride and its impurities using supercritical fluid chromatography.

Simultaneous separation of compounds with multiple chiral centers and highly similar structures presents significant challenges. This study developed a novel supercritical fluid chromatography (SFC) method with reduced organic solvent consumption and robust separation capabilities to address these challenges. The method was applied to simultaneously achieve enantioselective, diastereoselective, and achiral separation of palonosetron hydrochloride and its six impurities.

Preparation and optimization of dummy molecularly imprinted polymer-based solid-phase extraction system for selective enrichment of p-toluene sulfonate esters genotoxic impurities.

Sulfonate esters, one class of genotoxic impurities (GTIs), have gained significant attention in recent years due to their potential to cause genetic mutations and cancer. In the current study, we employed the dummy template molecular imprinting technology with a dummy template molecule replacing the target molecule to establish a pretreatment method for samples containing p-toluene sulfonate esters. Through computer simulation and ultraviolet-visible spectroscopy analysis, the optimal functional monomer acrylamide and polymerization solvent chloroform were selected.

A cell-based assay to discover inhibitors of Zika virus RNA-dependent RNA polymerase.

Zika virus (ZIKV) belongs to Flaviviridae, the Flavivirus genus. Its infection causes congenital brain abnormalities and Guillain-Barré syndrome. However, there are no effective vaccines, no FDA-approved drugs to manage ZIKV infection.

A novel multi-hyphenated approach to screen and character the xanthine oxidase inhibitors from saffron floral bio-residues.

Recently, the incidence of hyperuricemia increased with patient rejuvenation, searching for new xanthine oxidase (XOD) inhibitors from natural products becomes important. In our previous work, a flavonoid extract of saffron floral bio-residues (SFB) was found to alleviate hyperuricemia via inhibiting XOD. In this study, an integrated approach combining two-dimensional liquid chromatography, surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC) was developed to online screen and character the potential XOD inhibitors from SFB.

Teicoplanin derivatives block spike protein mediated viral entry as pan-SARS-CoV-2 inhibitors.

The rapid emergence of highly transmissible SARS-CoV-2 variants poses serious threat to the efficacy of vaccines and neutralizing antibodies. Thus, there is an urgent need to develop new and effective inhibitors against SARS-CoV-2 and future outbreaks. Here, we have identified a series of glycopeptide antibiotics teicoplanin derivatives that bind to the SARS-CoV-2 spike (S) protein, interrupt its interaction with ACE2 receptor and selectively inhibit viral entry mediated by S protein.

Halogenase-Targeted Genome Mining Leads to the Discovery of (±) Pestalachlorides A1a, A2a, and Their Atropisomers.

Genome mining has become an important tool for discovering new natural products and identifying the cryptic biosynthesis gene clusters. Here, we utilized the flavin-dependent halogenase GedL as the probe in combination with characteristic halogen isotope patterns to mine new halogenated secondary metabolites from our in-house fungal database. As a result, two pairs of atropisomers, pestalachlorides A1a (1a)/A1b (1b) and A2a (2a)/A2b (2b), along with known compounds pestalachloride A (3) and SB87-H (4), were identified from Pestalotiopsis rhododendri LF-19-12.

Repurposing of the antihistamine mebhydrolin napadisylate for treatment of Zika virus infection.

Zika virus (ZIKV) infection can lead to severe neurological disorders and fetal defects, which has become a public health problem worldwide. However, effective clinical treatment for ZIKV infection was still arduous. Antihistamines are attractive candidates for drug repurposing due to their low price and widespread availability.

Application of Transmission Raman Spectroscopy in Combination with Partial Least-Squares (PLS) for the Fast Quantification of Paracetamol.

In recent years, transmission Raman spectroscopy (TRS) has emerged as a potent new tool for rapid, nondestructive quantitation in pharmaceutical manufacturing. In order to expand the applicability of TRS and enhance its use in product quality monitoring during drug production, we aimed, in the present study, to apply partial least-squares (PLS) approaches to build a model consisting of 150 handmade tablets and covering 15 levels through the use of a multifactor orthogonal design of experiment (DOE), which was used to predict concentrations of validation tablets made by hand. The difference between results according to HPLC and TRS were negligible.

A DasA family sugar binding protein Ste2 links nutrient and oxidative stress to exopolysaccharides production in Streptomyces sp. 139.

Background: Ebosin is an exopolysaccharide produced by Streptomyces sp. 139, and its biosynthetic gene cluster (ste) has been previously described. Ste234 has high homology to the well-known ATP-binding cassette transport system DasABC, which has been linked to the regulation of morphological differentiation, antibiotics biosynthesis and aminosugars utilization in Streptomycetes.

Identification of miRNA and Their Regulatory Effects Induced by Total Flavonoids From in the Treatment of Vascular Dementia.

Vascular dementia (VaD) is a general term used to describe difficulties in memory, reasoning, judgment, and planning caused by a reduced blood flow to the brain and consequent brain damage, in which microRNAs (miRNAs) are involved. L. () is traditionally used in the treatment of cardiovascular diseases as well as VaD, but the biomolecular mechanisms underlying its therapeutic effect are obscure.

Separation of chiral and achiral impurities in paroxetine hydrochloride in a single run using supercritical fluid chromatography with a polysaccharide stationary phase.

Separating paroxetine hydrochloride and its impurities using conventional reversed-phase liquid chromatography (RPLC) is challenging due to their highly similar structures. In the present study, a rapid, simple, sensitive and environmentally friendly method was developed for the determination of chiral and achiral impurities in raw materials of paroxetine hydrochloride using chiral supercritical fluid chromatography (SFC). The impacts of chiral stationary phases (CSPs), mobile phases, column temperature and back pressure on the retention and separation of analytes were comprehensively evaluated.

Impurity profiling of Compound Amino Acid Injection (6AA) using ion-pair high performance liquid chromatography coupled with corona-charged aerosol detection and high resolution mass spectrometry.

The complex industrial production process of amino acids (AAs) leads to the existence of a certain amount of impurities in Compound Amino Acid Injection (6AA). It is difficult to obtain its comprehensive and systematic impurity profile using conventional ultraviolet (UV) detectors due to lack of a suitable chromophore in the structures of AAs and their impurities. In our study, a universal ion-pair high performance liquid chromatography (HPLC) method combined with high resolution mass spectrometer (HRMS) and charged aerosol detection (CAD) was developed to identify and determine the content of impurities in Compound Amino Acid Injection (6AA), respectively.

Recent advances in research of colchicine binding site inhibitors and their interaction modes with tubulin.

Microtubules have been a concerning target of cancer chemotherapeutics for decades, and several tubulin-targeted agents, such as paclitaxel, vincristine and vinorelbine, have been approved. The colchicine binding site is one of the primary targets on microtubules and possesses advantages compared with other tubulin-targeted agents, such as inhibitors of tumor vessels and overcoming P-glycoprotein overexpression-mediated multidrug resistance. This study reviews and summarizes colchicine binding site inhibitors reported in recent years with structural studies via the crystal structures of complexes or computer simulations to discover new lead compounds.

Blocking Effect of Demethylzeylasteral on the Interaction between Human ACE2 Protein and SARS-CoV-2 RBD Protein Discovered Using SPR Technology.

The novel coronavirus disease (2019-nCoV) has been affecting global health since the end of 2019, and there is no sign that the epidemic is abating. Targeting the interaction between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and the human angiotensin-converting enzyme 2 (ACE2) receptor is a promising therapeutic strategy. In this study, surface plasmon resonance (SPR) was used as the primary method to screen a library of 960 compounds.

Discovery of indolyl-containing peptides as novel antibacterial agents targeting tryptophanyl-tRNA synthetase.

There is an urgent need for antibiotics with novel structures and unexploited targets to counteract bacterial resistance. Novel tryptophanyl-tRNA synthetase inhibitors were discovered based on virtual screening, surface plasmon resonance binding, enzymatic activity assay and antibacterial activity evaluation. Of the 29 peptide derivatives tested for antibacterial activity, some inhibited the growth of both and .

A self-assembled electrochemical immunosensor for ultra-sensitive detection of ochratoxin A in medicinal and edible malt.

Trace residue of mycotoxins in complex medicinal and edible food matrices has brought huge challenges for the development of ultrasensitive analytical methods. Here, a green electrochemical immunosensor for the ultrasensitive detection of ochratoxin A (OTA) was fabricated by self-assembling a compact 2-mercaptoacetic (TGA) monolayer on the surface of the working Au electrode to form the Au/TGA/bovine serum aibumin (BSA)-OTA/anti-OTA monoclonal antibody composite probes for selective and ultra-sensitive detection of OTA based on indirect competitive principle and differential pulse voltammetry analysis. The electrochemical impedance spectroscopy and cyclic voltammetry methods were introduced to characterize the assemble situation of the TGA-modified Au electrode and optimize some critical parameters for the green electrochemical immunoseonsor.

Five solvates of a multicomponent pharmaceutical salt formed by berberine and diclofenac.

A multicomponent pharmaceutical salt formed by the isoquinoline alkaloid berberine (5,6-dihydro-9,10-dimethoxybenzo[g]-1,3-benzodioxolo[5,6-a]quinolizinium, BBR) and the nonsteroidal anti-inflammatory drug diclofenac {2-[2-(2,6-dichloroanilino)phenyl]acetic acid, DIC} was discovered. Five solvates of the pharmaceutical salt form were obtained by solid-form screening. These five multicomponent solvates are the dihydrate (BBR-DIC·2HO or CHNO·CHClNO·2HO), the dichloromethane hemisolvate dihydrate (BBR-DIC·0.

Polygala tenuifolia-Acori tatarinowii herbal pair as an inspiration for substituted cinnamic α-asaronol esters: Design, synthesis, anticonvulsant activity, and inhibition of lactate dehydrogenase study.

Inspired by the traditional Chinese herbal pair of Polygala tenuifolia-Acori Tatarinowii for treating epilepsy, 33 novel substituted cinnamic α-asaronol esters and analogues were designed by Combination of Traditional Chinese Medicine Molecular Chemistry (CTCMMC) strategy, synthesized and tested systematically not only for anticonvulsant activity in three mouse models but also for LDH inhibitory activity. Thereinto, 68-70 and 75 displayed excellent and broad spectra of anticonvulsant activities with modest ability in preventing neuropathic pain, as well as low neurotoxicity. The protective indices of these four compounds compared favorably with stiripentol, lacosamide, carbamazepine and valproic acid.

Determination of epoxide impurity in sarpogrelate hydrochloride intermediate by UHPLC and column-switching liquid chromatography.

The determination of genotoxic impurities, which is closely related to toxicological concern and daily dose, plays a key role in drug quality control. Epoxide impurity is a kind of genotoxic impurity with an epoxy ring structure during the synthesis process of sarpogrelate hydrochloride. According to the sarpogrelate hydrochloride daily dose, epoxide impurity is limited to the under 5 ppm level.

Fast simultaneous determination of main components and impurity sodium ion in PAMA injection by mixed-mode chromatography.

This study describes an analytical method to control the quality of potassium aspartate and magnesium aspartate (PAMA) injection based on the simultaneous detection of the main components (K, Mg and Asp) and impurities (Na) using a mixed-mode chromatography coupled with charged aerosol detector. To obtain optimal chromatographic separation, the effects of organic content, column temperature, buffer types, pH and concentrations were evaluated. A Response Surface Methodology (RSM) optimal design was performed after single factor experiment.

A direct determination of AFBs in vinegar by aptamer-based surface plasmon resonance biosensor.

Aflatoxin (AFB) is one of the most toxic fungal metabolites produced by Aspergillus flavus, which may contaminate food and agricultural products. Herein, an aptamer-based surface plasmon resonance (SPR) biosensor was developed to detect AFBs. The chosen aptamer showed comparable interaction with the two AFBs, namely aflatoxin B1 (AFB1) and aflatoxin B2 (AFB2).

Molecular background of the regional lymph node metastasis of gastric cancer.

Gastric cancer (GC) is one of the deadliest types of cancer in the world. Lymph node (LN) metastasis is a complex and malignant behavior of GC, involving a sequence of biological processes, including decreased adherence to adjacent cells, extracellular matrix (ECM) degradation and lymphatic channel permeation. LN metastasis is directly associated with the treatment response, local recurrence and long-term survival of patients with GC.

[Determination of succinic acid in desvenlafaxine succinate by high performance ion-exclusion chromatography and high performance ion-exchange chromatography].

New methods were developed for the determination of succinic acid in desvenlafaxine succinate (DVS) by high performance ion-exclusion chromatography (HPIEC) and high performance ion-exchange chromatography (HPIC). HPIEC and HPIC methods were used separately to determinate the succinic acid in DVS. With HPIEC, the sample was diluted with 2.