Combinatorial Chemistry & High Throughput Screening - Volume 26, Issue 15, 2023

2-Arylpropionic acid nonsteroidal anti-inflammatory drugs (NSAIDs) provide one of the most demonstrated pharmaceutical examples of chiral inversion. Chiral inversion depends on various factors (viz. biological-, solvent-, light-, temperature-induced, etc.) and the energy barrier associated with the stereogenic element present in the chiral molecule. The pharmacological properties of chiral drugs depend on the activity of one enantiomer or both the enantiomers targeting different biological targets. Consequently, chiral inversion can alter the biological activities of the pharmaceutical drug. Hence a better understanding of chiral inversion, factors facilitating such inversion, and the tools employed to determine chiral inversion are of great significance from a pharmacological and toxicological perspective.

The recent development of monolithic chiral stationary phases (CSPs) for liquid chromatography (LC) is mainly focused on reducing backpressure, maximizing flow rates, faster run time, column efficiency, and stability. This review paper emphasizes recent progress in the development of polysaccharide and cyclodextrin-based monolithic CSPs. Further the paper draws attention to competing techniques, like non-porous particle-packed columns, core-shell and monoliths as chromatographic support matrix, available for achieving fast and efficient chromatographic separation. A brief discussion on the three main classes of chiral monolithic stationary phase viz. silica, organic polymer and hybrid-based monolithic stationary phases is also presented. In addition, the paper highlights various studies on the application of monolith chiral CSPs in LC and capillary electrochromrography separation and analysis of chiral compounds.

Biogenic amines (BAs) are compounds deemed to be foodstuff contaminants and are the cause of poisoning or allergy. The main BAs found in foods include histamine, tyramine, putrescine, cadaverine, spermine and spermidine. The number of poisoning cases related to BAs in food has increased, which is reinforcing the need for BAs detection to ensure food safety. BAs are found in varying quantities in different foods such as fish, fruits, meat, cheese, vegetables, beer, and wine. Currently, different analytical techniques are used for BAs detection, as well as sample treatment methods that allow greater sensitivity, higher analyzing speed and lower detection limits. Moreover, BAs can be precursors of nitrosamines, which have been associated with mutagenic and carcinogenic activity. This review aims to provide a general approach to the different detection techniques of the BAs in foods, their concentrations and treatment methods.

Drug degradation is a process that can render pharmaceuticals inactive without causing any visible distortion. This can disrupt the therapeutic process, and on occasion, when the process produces toxic metabolites, it can have much more fatal consequences. Light is one of the most significant components that might cause deterioration, and several attempts have been made to improve and increase the practical photosensitizing of nano-scaled pharmaceuticals. Considering this, the insolubility and aggregating qualities of fullerenes have received significant attention. Fullerene is considered to have a unique carbon structure. In order to gain improved water solubility and biocompatible properties, fullerenes have been combined with water-soluble, biodegradable, and adjustable polymers. More specifically, these linkers exhibit increased tumor cell identification and greater tumor cell suppression when linked to therapeutic ligands (tumor-targeting) or stimuliresponsive polymers. According to scientific studies, fullerene-drug combinations can be used in certain complex diseases, like infectious and viral types. Several studies have combined fullerenes into nano-emulsions or liposomes for various pharmacological objectives. In the current work, fullerene/polymer nanomaterials are discussed for potential therapeutic techniques for the treatment of various diseases, particularly cancer and AIDS. According to the research studies, fullerene is a suitable element with outstanding physical and chemical properties that has a wide range of potential applications in the pharmaceutical industry, including drug delivery system design, photodynamic cancer therapy, and antioxidant therapy.

The electrochemical detection of neurotransmitters is an imperative application in the field of analytical chemistry. The recent development in the electrochemical sensors based on carbon electrodes is very important due to their sensitivity and simplicity. Using the carbon-based sensor for the electrochemical analysis of the neurotransmitters is a simple method. Furthermore, these above methods provide high sensitivity, are user-friendly, and are well-matched with the concept of green chemistry. In light of this matter, this review article is devoted to the voltammetric detection of neurotransmitters by using the carbon-based electrode. Here, we survey the accomplishments in the determination of numerous neurotransmitters with high selectivity and sensitivity provided using carbon-based electrodes. Attention is concentrated on the working electrode and its promising modification which is vital for further analysis of the neurotransmitters.

Rice (Oryza sativaL.), a cereal grass, belongs to the genus Oryzafrom the family Poaceae, which encompasses twenty-five species cultured in many countries of Asia, and partly in the rest of the world. From these species, two viz. Oryza sativa(O. sativa.) Asian rice and Oryza glaberrima. (O. glaberrima.) African rice are commonly found and the most widely consumed staple food by a large part of the human population in the world, especially in Asia due to their nutritional and nutraceutical prospects. Rice, a popular source of carbohydrates, also contains a good amount of dietary fiber, minerals (Ca, Zn, Se, P, K, Mg, Fe, and Mn), protein and vitamin B along with several other medicinally important bioactives such as tocols (α-tocopherols and α-tocotrienols) (ßsitosterol) phenolic acids, flavonoids (apiginine), and oryzanol (24-Methylenecylcoartanyl transferulate). Rice bran is a byproduct of the rice polishing industry and is valuable in terms of containing 15-20% high-value oil. Because of the natural antioxidants present in rice, several medicinal benefits and biological properties can be attributed to rice consumption. The nutrient profile of rice varies based on several factors, such as grains (white, brown, red, and black/purple), the extent of polishing, and the preparation method. Considering the importance of rice as a traditional diet rich in high-value bioactives, together with the existing gap of related information, it is worthwhile to assemble a comprehensive review that focuses on the detailed profile of valuable nutrients and high-value phytochemicals and biological activities of rice to explore its functional food and nutraceutical applications. This review attempts to provide collective information on the essential rice cereal for its nutritional and antioxidant potential.

Mepivacaine, an amide-type local anesthetic drug widely used in regional anesthesia, was studied by some aspects such as electrochemical behavior, mechanism illumination, and analytical applications by cyclic voltammetry (CV) and different pulse voltammetry (DPV) methods. In this study, a novel, fast, simple, portable, and the inexpensive electrochemical sensor was developed for the determination of mepivacaine. This study was carried out by mepivacaine anodic direction detection for the first time. The modified sensor was fabricated with silver nanoparticles (AgNP) and multiwalled carbon nanotubes paste electrode (MWCNTPE) by using the drop-dry method. Different experimental parameters, such as pulse amplitude, step potential, and scanning rate in the DPV application module, were optimized. Under optimal operation conditions, the limit of detection (LOD) as low as 31 μg L^-1 was found over the dynamic range (0.1–8.0 mg L^-1). In contrast to its high response towards mepivacaine, the DPV exhibits negligible responses on modified AgNP/MWCNTPE when exposed to interfering species such as dopamine, uric acid, glucose, ascorbic acid, and some heavy metals. Exceptionally, the proposed DPV method on modified AgNP/MWCNTPE was successfully applied to pharmaceutical dosage form and synthetic human serum with a low relative standard deviation (RSD) of 1.35% and 2.02%, respectively.

Introduction: In drug analysis, using non-hazardous solvents instead of the ones harmful to humans and the environment is a green strategy to protect analysts and environmental health. Objective: Procainamide (PCA) is an antiarrhythmic drug requiring therapeutic drug monitoring (TDM) because of its narrow therapeutic window and serious side effects. Aim: The aim of this study is to develop validated green HPLC methods to be used in drug quality control and TDM analysis for PCA, thus indicating the further applicability in the analysis of TDM-required drugs, such as immunosuppressants, anti-cancer drugs, and psychiatric drugs. Methods: Human-friendly ethanol was selected as an organic solvent in the mobile phase. PCA was eluted from NUCLEODUR 100-5 C8 ec (5 μm, 150 x 4.6 mm) column by a mobile phase containing ethanol and 50 mM NaH2PO4buffer (5:95, v/v). The mobile phase flow rate was 1.0 ml min^-1, the column temperature was 35 °C, and the wavelength at the PDA detector was 278 nm. Results: Retention time for PCA was 5.0 min and 7.7 min for paracetamol as an internal standard (IS). In the green HPLC method for pharmaceutical analysis, the highest relative standard deviation (RSD) and mean recovery values were 1.32% and 98.89%, respectively. In the analysis of plasma, the sample preparation step was only smooth protein precipitation by ethanol. Thus, the bioanalytical method was fully green having a limit of detection (LOD) of 0.3 μg ml^-1 and a limit of quantification (LOQ) of 0.8 μg ml^-1. The therapeutic plasma concentration for PCA was reported in the range of 4–12 μg ml^-1. Conclusion: As a result, the green HPLC methods developed and validated in this study were selective, accurate, precise, reproducible, and trustable and have the quality for the application in pharmaceutical and TDM analysis of PCA, thus encouraging green HPLC analysis of other TDM required drugs.

PCSK9 (proprotein convertase subtilisin/kexin type 9) is an enzyme that helps to reduce cardiovascular events. This clinical result is attributable primarily to the crucial involvement of PCSK9 in regulating the low-density lipoprotein cholesterol level. Because oral anti-PCSK9 medications have yet to be available, the benefits of this unique treatment approach have been diminished. Identifying naturally occurring PCSK9 inhibitors may lead to considerable progress in this regard. These inhibitors serve as a starting point for producing oral and effective components that could be used with statins to boost the proportion of patients who achieve their LDL-cholesterol goals. In this review, we have briefly summarised the recent information regarding natural components or extracts that have been shown to inhibit PCSK9 activity.

Background: Bioautography is a technique for the detection of biological activity that combines the elements of planar chromatography. Its hyphenated variants are widely used in the screening of natural products possessing biological activity. It can be used in the activity-based screening of phytochemical ingredients by employing various enzyme processes and reactions and facilitates the rapid determination of bioactive compounds in pant samples. Objective: To give a comprehensive overview of effect-directed assays and biological detection approaches used in conjugation with thin layer chromatography technique. The present review article attempts to throw light on the various aspects of bioautography, including its types and applications, thereby giving its concise overview and its relevance in the field of natural product screening. Methods: Various search engines were used for the literature survey, including Google Scholar, Semantic Scholar, PubMed, ResearchGate and Scopus. Results: Bioautography has wide-ranging uses in the screening of compounds such as antioxidants, antifungals, antimicrobials, estrogenic, antitumors, and various enzyme inhibitors compounds like α and β-glucosidase inhibitors and α-amylase inhibitors. Conclusion: Bioautography serves to be an effective tool for the isolation of bioactive phytochemicals, thereby allowing us to scientifically validate the biological activities of various compounds, which can then be utilized for making potent medications for various diseases.

Background: Dendrobium nobileLindl. (DNL) is effective for the treatment of alcoholic liver disease (ALD), but the underly mechanism is still unclear. Objectives: This research aimed to investigate the effects and mechanism of the aqueous extract of Dendrobium nobileLindl (AEDNL) in ALD rats based on a metabolomics approach. Materials and Methods: In this study, 18 Sprague-Dawley male rats were randomly divided into control, model, and AEDNL groups (n=six). Rats in the AEDNL group were given AEDNL (152 mg/kg) intragastric administration from the first day for 30 consecutive days. From day 15 to day 30, model and AEDNL groups were given 30% ethanol (10 ml/kg) after 4 h of daily administration. Then, serum and liver samples were collected for biochemical analysis, histopathological examination, and Ultra Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry (UPLC-Q-TOF/MS) determination for metabolomic analysis. Results: Compared with the model group, the liver/body weight index and serum levels of TC, LDL-C, and TBIL in the AEDNL group were significantly decreased. Hepatocyte cord arrangement, hepatocyte balloon, and fat vacuolization were significantly improved in the AEDNL group. Metabolism profiles were changed in the model and AEDNL groups. Seven and two common differential metabolites (Guanosine3',5'-cyclic monophosphate, and Glutaric acid) were found in serum and liver, respectively. In addition, the hepatoprotective effect of AEDNL on ALD was related to steroid hormone biosynthesis, riboflavin metabolism, and glycerophospholipid metabolism. Conclusion: The research could provide novel evidence of the protective effects of AEDNL on ALD.

Aim: To determine whether or not a decoction made from Qigu Zhushui has a suppressive impact on malignant ascites in mice. Background: Malignant ascites are one of the common complications of advanced malignant tumors. Patients with malignant ascites typically have a poor prognosis, with only 12 to 20 weeks of survival. Currently, the standard treatments for malignant ascites are systemic chemotherapy, which is ineffective in eradicating the disease and is associated with issues such as safety, short duration of sustained high-level drug concentration in localised regions, and drug resistance. Objective: To clarify the effect of Qigu Zhushui decoction on inhibiting malignant ascites in mice and provide the experimental basis for further research. Methods: The ascites model of liver cancer in mice was established by intraperitoneal injection of the H22-H8D8 cell line of liver cancer. ELISA detected the content of CEA, VEGF and TNF-α in ascites. Results: Qigu Zhushui decoction combined with cisplatin group and Qigu Zhushui decoction highdose group could significantly reduce the weight, abdominal circumference and ascites volume of mice, and their survival days and survival rate were also greatly improved; The levels of CEA and VEGF in the combination group decreased significantly, while the level of TNF-α increased; The level of TNF-a in the high dose group of Qigu Zhushui decoction was significantly increased, while the level of CEA and VEGF in the moderate dose group was decreased. Conclusion: Qigu Zhushui decoction can reduce the malignant ascites in mice, and the combination of Qigu Zhushui decoction and cisplatin has a significant anti-malignant ascites effect, which can significantly prolong the survival time and improve the survival rate.

Background: Acute Liver Failure (ALF) is a difficult problem to solve in clinical practice. The presence of non-SMC condensin I complex subunit G (NCAPG) has previously been linked to vascular invasion of digestive system tumors, foreshadowing poor prognosis. Its role in ALF biology, however, remains unknown. This article explores the role of NCAPG as a potential biomarker candidate for the accurate diagnosis and targeted treatment of ALF. Methods: The study included transcription data (GSE14668, GSE38941, GSE62029, GSE96851, and GSE120652) of ALF, normal tissues, and clinical samples, where NCAPG was selected as the differential gene by the “DESeq2” R package to analyze the immune cell functions and signal pathways. Furthermore, RT-qPCR and Western blot analyses were used to confirm the RNA and protein levels of NCAPG in ALF cell models, respectively. Results: Bioinformatics analysis revealed that NACPG was up-regulated in ALF tissues, and the functional signaling pathway was primarily associated with immune infiltration. Based on the results of clinical samples, we suggest that NCAPG was overexpressed in ALF tissues. We also found that the expression of NCAPG increased with the degree of liver injury in vitro. Enrichment analysis suggested that NCAPG influenced ALF as a PI3K/AKT pathway activator. Conclusion: Our study suggests that NCAPG is a preliminary tool for the diagnosis of ALF. It can affect ALF via the PI3K/AKT pathway and is a potential therapeutic target to improve prognosis.