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Objective: The aim of this study was to synthesize azine analogues of 1,2-diphenylethan-1-one while assessing their ability to scavenge free radicals with DPPH. In order to explore these compounds' potential as novel antioxidant agents with possible applications in the pharmaceutical, neutraceutical, and other industries, we synthesized them. Methods: The initial steps involved reacting 1,2-diphenylethan-1-one and additional amount of hydrated hydrazine in an ethanol solvent to produce the needed hydrazone, which paved the way for a two-step reaction that produced azine derivatives. Ultimately, a number of substituted aldehydes that are aromatic were heated by reflux condition, catalyzed by acetic acid with the obtained hydrazone to produce the azine derivatives in high yields. Results: These synthetic derivatives were screened for their anti-oxidant activity, compound (IIe) (IC50 = 24.13 ± 0.27 µM), (IIf) (IC50 = 29.11 ± 0.41 µM), and (IIg) (IC50 = 31.12 ± 0.44 µM) attributed the most excellent activity, however compound (IIc) and (IId) were found as significant DPPH free radical scavenging agents with IC50 values 46.21 ± 0.12 and 49.23 ± 0.54 µM, respectively while compound (IIa) and (IIb) displayed less anti-oxidant effect with IC50 values 55.11 ± 0.24 and 66.21 ± 0.12 µM. Conclusions: The study shows that the azine derivatives under investigation have promising potential as synthetic antioxidants due to their significant DPPH radical scavenging action. Furthermore, compounds containing electron-donating groups exhibit antioxidant activity comparable to that of ascorbic acid, an antioxidant that occurs naturally. These findings highlight the antioxidant qualities of the synthetic azine derivatives and suggest potential applications as medical treatments for oxidative stress-related illnesses. [ABSTRACT FROM AUTHOR]

In this study, we demonstrate the successful synthesis of sulfur–MOF composites and their application in the Willgerodt–Kindler reaction. We showed that MIL-53(Al), CAU-10-H and MIL-101(Cr) encapsulate the sulfur without MOF decomposition by the melt-diffusion technique, whereas MIL-88A and MIL-101(Fe) were unable to form S@MOF composites. Various techniques, including XRD, SEM, EDS, and porometry, were used to characterize the synthesized S@MOF composites. The influence of MOF nature, temperature, reaction time and reagent ratio on the Willgerodt–Kindler reaction product formation was evaluated. The S@CAU-10-H composite led to the thiomorpholides from various arylaldehydes, acetophenones and propiophenones in 56–91% isolated yields. The reaction proceeds at near equimolar reactant concentrations. Product isolation is straightforward and does not require tedious chromatographic purification. The MOF was easily separated and reused in five runs, achieving a good performance without significant framework degradation. We postulate that the MOF has multiple roles, acting as a reaction medium, sulfur carrier, amine absorber and dehydration agent. [ABSTRACT FROM AUTHOR]

Yam (Dioscorea alata L.) contains various compounds that are widely known to have various health benefits. This study aims to analyze the toxicity of the active compounds in D. alata L. in silico. This involves the screening of the bioactive compounds, drug-likeness screening based on the Lipinski rule of five, and toxicity prediction using ADMETSAR (ADMET) and Protox II (hepatotoxicity, immunotoxicity, mutagenicity, and cytotoxicity). The bioactive compounds in D. alata L were 64 obtained from the Kanava Knapsack and the USDA database. 23 of these compounds with potential as drugs include 6 flavonoids compounds (26.09%), 5 stilbenoid compounds (21.74%), 4 glycosides compounds (17.39%), 3 carboxylic acid compounds (13.04%), vitamins (8.69%), phenol, propiophenone and steroid (4.35%). Based on the results of LD-50, there were 2 non-toxic compounds: diosgenin and catechin. While other compounds were classified as having a low toxicity. There are 2 compounds predicted to have Human Hepatotoxicity activity, 14 compounds that have drug-induced liver injury activity, 2 hepatotoxicity compounds, 5 carcinogenicity compounds, 6 immunotoxicity compounds, 2 mutagenicity compounds, and 1 cytotoxicity compound. The toxicity is predicted to appear if used as a single compound. This study proved that most of the active compounds in D. alata L. possess very low toxicity with only 2 non-toxic compounds (catechin and diosgenin). However, the use of the compounds as a single compound is predicted to have some toxic activities. It is important to carry out further research to validate the toxicity of the active compounds D. alata L. in vivo. [ABSTRACT FROM AUTHOR]

BACKGROUND Lumbodorsal fasciitis (LF) is a condition in which muscle and fascial lesions cause low back pain (LBP) and limited mobility. This retrospective study aimed to explore the efficacy and safety of ultrasound-guided fascial hydrodissection combined with eperisone for treating LF. MATERIAL AND METHODS A total of 103 patients with LF were selected and divided into a combined therapy (CT) group (ultrasound-guided fascial hydrodissection and oral drugs of eperisone) and single medication (SM) group (oral drugs of celecoxib and eperisone). Outcomes were evaluated using the visual analog scale (VAS) and Oswestry disability index (ODI) at baseline and at 2 weeks, 1 month, and 3 months after treatment. The adverse reactions and complications of the 2 groups were recorded. RESULTS There were no significant differences in the baseline characteristics of the 2 groups (P>0.05). After treatment, all scores showed a statistically significant improvement at 2 weeks and 1 month (P<0.05). The VAS and ODI scores showed a significant effect by time and group (P<0.001). The results also showed significant group-by-time interactions (P<0.001). Patients in the CT group had lower scores at any follow-up time (P<0.05). At 3 months, the scores slightly increased. There were no adverse reactions or complications in the CT group; however, the SM group had 4 cases of gastrointestinal reactions. CONCLUSIONS Ultrasound-guided fascial hydrodissection combined with eperisone therapy can effectively relieve LBP and improve lumbar function in treating LF. Moreover, this procedure is considered safe.

Drug checking is a harm reduction measure that provides people with the opportunity to confirm the identity and purity of substances before consumption. The CanTEST Health and Drug Checking Service is Australia's first fixed-site drug checking service, where clients can learn about the contents of the samples they provide while receiving tailored harm reduction and health advice. Three samples were recently presented to the service with the expectation of 4-fluoromethylphenidate (4F-MPH) 1, methoxetamine (MXE) 2 and 3-methylmethcathinone (3-MMC) 3. The identity of all three samples did not meet these expectations and remained unknown on-site, as no high confidence identifications were obtained. However, further analysis by nuclear magnetic resonance spectroscopy, high resolution gas chromatography-electron ionisation-mass spectrometry and liquid chromatography-electrospray ionisation-mass spectrometry at the nearby Australian National University allowed for the structure elucidation of the three samples as 4-fluoro-α-pyrrolidinoisohexanophenone (4F-α-PiHP) 4, 1-(4-fluorobenzyl)-4-methylpiperazine (4F-MBZP) 5 and N-propyl-1,2-diphenylethylamine (propylphenidine) 6, respectively. Given all three samples were not of the expected identity and have not yet been described as new psychoactive substances in the literature, this study presents a full characterisation of each compound. As exemplified by this rapid identification of three unexpected new psychoactive substances, drug checking can be used as an effective method to monitor the unregulated drug market., (© 2024 The Authors. Drug Testing and Analysis published by John Wiley & Sons Ltd.)

Synthetic cathinones, which are novel psychoactive substances, have caused major social problems worldwide. A substance called 2-methyl-4′-(methylthio)-2-morpholinopropiophenone (MMMP), which is employed as a commercial industrial photoinitiator for triggering polymerization, has a basic cathinone backbone; however, few reports regarding MMMP have been published. In the current study, three potential metabolites of MMMP—namely hydroxy-MMMP (HO-MMMP), HO-MMMP-sulfoxide (HO-MMMP-SO), and HO-MMMP-sulfone (HO-MMMP-SO 2)—were successfully synthesized, and MMMP and these three potential metabolites were used as standards to establish an analytic method based on liquid chromatography–tandem mass spectrometry for the quantitative analysis of urine. This analytic method and related parameters—including dynamic range, limit of quantification, selectivity, precision, accuracy, carryover effect, matrix effect, interference, and dilution integrity—were optimized and validated. Forty urine samples from 1,691 individuals who abused drugs were determined to contain MMMP, HO-MMMP, HO-MMMP-SO, or HO-MMMP-SO 2 ; the results of this study indicate that approximately 2.37 % of drug abusers in Taiwan consumed MMMP in 2023. These 40 urine samples were analyzed to investigate the metabolism of MMMP in humans. The results indicate that HO-MMMP-SO is the main metabolite in human urine. This study recommends HO-MMMP-SO with a concentration of 2 ng/mL as a target and cutoff value, respectively, for identifying individuals who have consumed MMMP. [Display omitted] ● MMMP metabolites including HO-MMMP, HO-MMMP-SO, and HO-MMMP-SO 2 were successfully synthesized as standard chemicals. ● An LC-MS/MS assay was established for the detection of MMMP and its metabolite. ● HO-MMMP-SO is the major metabolite of MMMP in human urine. [ABSTRACT FROM AUTHOR]

Inherited deficiency in the mitochondrial protein frataxin (FXN) causes the rare disease Friedreich's ataxia (FA), for which there is no successful treatment. We identified a redox deficiency in FA cells and used this to model the disease. We screened a 1600-compound library to identify existing drugs, which could be of therapeutic benefit. We identified the topical anesthetic dyclonine as protective. Dyclonine increased FXN transcript and FXN protein dose-dependently in FA cells and brains of animal models. Dyclonine also rescued FXN-dependent enzyme deficiencies in the iron-sulfur enzymes, aconitase and succinate dehydrogenase. Dyclonine induces the Nrf2 [nuclear factor (erythroid-derived 2)-like 2] transcription factor, which we show binds an upstream response element in the FXN locus. Additionally, dyclonine also inhibited the activity of histone methyltransferase G9a, known to methylate histone H3K9 to silence FA chromatin. Chronic dosing in a FA mouse model prevented a performance decline in balance beam studies. A human clinical proof-of-concept study was completed in eight FA patients dosed twice daily using a 1% dyclonine rinse for 1 week. Six of the eight patients showed an increase in buccal cell FXN levels, and fold induction was significantly correlated with disease severity. Dyclonine represents a novel therapeutic strategy that can potentially be repurposed for the treatment of FA.

Abstract Background The root of Baliospermum montanum has been used as an ingredient of traditional Thai medicines for the treatments of several diseases including itching eczema, muscle and joint inflammation, and cancer. Few studies have been done on phytochemical components of this root. In this study, we isolated major compounds of the crude ethanolic extract of B. montanum root and developed and validated a high performance liquid chromatographic (HPLC) method for the determination of its major components. We then investigated anti-allergic, anti-inflammatory and cytotoxic activities of the extract. Methods The aims of this study were to investigate in vitro activities including inhibitory effect of β-hexosaminidase released from RBL-2H3 cells, inhibition of nitric oxide (NO) production from RAW 264.7 cells and cytotoxic activity against cancerous liver cell lines (HepG2 and KKU M156) by using sulforhodamine B (SRB) assay. Isolation of major components was conducted by using column chromatographic method. Isolated major compounds were analyzed by using high performance liquid chromatography (HPLC). Results The crude extract exhibited the highest cytotoxic activity, with IC50 less than 1 μg/mL, while its anti-allergy and anti-inflammation were also potent with IC50 less than 6 μg/mL. Three propiophenones isolated from B. montanum root exhibited moderate cytotoxic activities (IC50 > 20 μg/mL). Two of the propiophenones found were major components that can be detected by HPLC. The developed and validated HPLC method showed good accuracy, precision, and linearity. Conclusion The results of this study suggested that ethanolic extract of of B.montanum root can be a potential source of anti-allergy, anti-inflammation, and anti-cancer compounds. The isolated compounds can serve as markers when B. montanum is used in herbal remedies but not as overall responsive markers. The HPLC method developed may be useful for quality control in the production of the extract and for further formulation developments. However, investigation of several associated biological activities is necessary before the development can proceed further. Minor active compounds should be isolated and a more sensitive analytical method should be developed to detail the key responsive components of the ethanolic extract of B. montanum root.

Forensic laboratories are constantly required to identify new drugs and their metabolites. N-ethylhexedrone (NEH, HEXEN), N-Ethylpentedrone (NEP), and 4-Chloromethcathinone (4-CMC, clephedrone) are synthetic substances structurally related to natural cathinone, alkaloid present in the leaves of the Catha edulis (Khat) plant. These synthetic cathinones (SC) are members of the heterogenous family of new psychoactive substances (NPS) that raised major concerns in scientific and forensic communities over the past years due to their widespread consumption. In this context, we investigated their metabolic profile using of UHPLC-QTOF-HRMS to elucidate the distribution of the parent drug and its metabolites in urine samples over time. Initially, both male and female volunteers were divided into three groups and eight subjects of each group were administered intranasally or orally with one SC (20-40 mg of NEH or NEP intranasal, 100-150 mg of 4-CMC oral). Urine samples were collected at 0-2 and 2-4 or 2-5 h. Urine (50 μL) was diluted 1:2 with acetonitrile/methanol (95:5) and injected into the UHPLC-QTOF-HRMS. Phase-I and phase-II metabolites were identified on the basis of fragmentation patterns and exact masses. Several phase-I and glucuronide-phase-II metabolites were identified in urine samples. Keto group reduction, hydroxylation and dealkylation were the common metabolic pathways identified for all cathinones and the presence of NEH-glucuronide, NEP-glucuronide and 4-CMC-glucuronide was also relevant. Significant is the slower metabolite formation for 4-CMC, which was detected at high concentrations in its original form even 5 h after administration, due to its long half-life and low intrinsic clearance compared to the other SCs. UHPLC-QTOF-HRMS demonstrated a considerable capability to semi-quantify the three synthetic cathinones and identify the target metabolites with high reliability. The introduction of new target compounds improves the efficiency of toxicological screening analysis on real samples and extends the window of detection of the SCs in biological matrices., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: As a canonical iron-dependent form of regulated cell death (RCD), ferroptosis plays a crucial role in chemical-induced liver injuries. Previous studies have demonstrated that xanthohumol (Xh), a natural prenylflavonoid isolated from hops, exhibits anti-inflammatory, anti-antioxidative and hepatoprotective properties. However, the regulatory effects of Xh on hepatic ferroptosis and the underlying mechanism have not yet been fully elucidated., Purpose: To investigate the hepatoprotective effects of Xh against drug-induced liver injury (DILI) and the regulatory effects of Xh on hepatic ferroptosis, as well as to reveal the underlying molecular mechanisms., Methods/study Design: The hepatoprotective benefits of Xh were investigated in APAP-induced liver injury (AILI) mice and HepaRG cells. Xh was administered intraperitoneally to assess its in vivo effects. Histological and biochemical studies were carried out to evaluate liver damage. A series of ferroptosis-related markers, including intracellular Fe 2+ levels, ROS and GSH levels, the levels of MDA, LPO and 4-HNE, as well as the expression levels of ferroptosis-related proteins and modulators were quantified both in vivo and in vitro. The modified peptides of Keap1 by Xh were characterized utilizing nano LC-MS/MS., Results: Xh remarkably suppresses hepatic ferroptosis and ameliorates AILI both in vitro and in vivo, via suppressing Fe 2+ accumulation, ROS formation, MDA generation and GSH depletion, these observations could be considerably mitigated by the ferroptosis inhibitor ferrostatin-1 (Fer-1). Mechanistically, Xh could significantly activate the Nrf2/xCT/GPX4 signaling pathway to counteract AILI-induced hepatocyte ferroptosis. Further investigations showed that Xh could covalently modify three functional cysteine residues (cys151, 273, 288) of Keap1, which in turn, reduced the ubiquitination rates of Nrf2 and prolonged its degradation half-life., Conclusions: Xh evidently suppresses hepatic ferroptosis and ameliorates AILI via covalent modifying three key cysteines of Keap1 and activating Nrf2/xCT/GPX4 signaling pathway., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled ‘Xanthohumol ameliorates drug-induced hepatic ferroptosis via activating Nrf2/xCT/GPX4 signaling pathway’., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Neurotoxicity induced by psychoactive substances is often accompanied by an imbalance of intracellular calcium ions. It is unclear whether calcium ions play a role in the toxicity induced by psychoactive substances. In the present study, we aimed to evaluate the occurrence of calcium dysregulation and its contribution to cytotoxicity in human neurotypic SH-SY5Y cells challenged with a recently developed psychoactive substance 4-methylethcathinone (4-MEC). An increase in the intracellular calcium was detected by inductively coupled plasma atomic emission spectrometry and Fluo-3 AM dye in SH-SY5Y cells after being treated with 4-MEC. The increase of intracellular Ca 2+ level mediated G0/G1 cell cycle arrest and ROS/endoplasmic reticulum stress-autophagy signaling pathways to achieve the toxicity of 4-MEC. In particular, N-acetyl-L-cysteine, a classical antioxidant, was found to be a potential treatment for 4-MEC-induced toxicity. Taken together, our results demonstrate that an increase in intracellular calcium content is one of the mechanisms of 4-MEC-induced toxicity. This study provides a molecular basis for the toxicity mechanism and therapeutic intervention of psychoactive substances., (© 2023 John Wiley & Sons Ltd.)

Avobenzone (AVO), an ultraviolet (UV) filter, is frequently used as an ingredient in personal cosmetics. This UV filter has been found to be easily exposed in swimming pools and beaches, and it has been detected in human urine and blood. Moreover, numerous studies have demonstrated that AVO exhibits endocrine-disrupting properties. Nevertheless, the effects of AVO on male fertility have not yet fully understood. Therefore, this study aimed to assess the effects of AVO on various sperm functions during capacitation. First, boar spermatozoa were treated with various AVO concentrations. After treatment, sperm motility and kinetic characteristics, capacitation status, intracellular adenosine triphosphate (ATP) levels, and sperm viability were evaluated. Moreover, Western blot analysis w.as conducted to evaluate protein kinase A (PKA) activity and tyrosine phosphorylation. As a result, AVO treatment significantly decreased total motility, progressive motility, and several kinetic characteristics at high concentrations (50 and 100 μM). Furthermore, the capacitation status dose-dependently decreased. Conversely, no significant differences in acrosome reaction, cell viability, and intracellular ATP levels were observed. However, the intracellular ATP level tended to decrease. In addition, AVO dose-dependently induced abnormal changes in PKA activity and tyrosine phosphorylation. Although AVO did not directly exert a toxic effect on cell viability, it ultimately negatively affected sperm functions through abnormal alterations in PKA activity and tyrosine phosphorylation. Thus, the potential implications on male fertility must be considered when contemplating the safe utilization of AVO., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Xanthohumol (XN), possessing potent physiological activity, is exclusively derived from hops (Humulus lupulus L.) and exhibits high instability. However, its inherent instability often results in degradation during storage, leading to a decline in its activity due to the formation of various products. This study aimed to explore the stability of XN in beer under different storage conditions, establish or clarify degradation kinetic models, and understand the degradation mechanism. Our findings revealed that XN would degrade rapidly when exposed to high temperature and light. Its degradation followed a first-order kinetic model, involving reactions such as isomerization, hydration and ortho-position cyclization, resulting in the formation of five products. These insights shed light on the factors and mechanisms underlying the instability and degradability of XN, serving as a foundation for the development of a stable beer product enriched with functional XN., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Ulcerative colitis (UC) is a chronic inflammatory disorder affecting the colon, with symptomatology influenced by factors including environmental, genomic, microbial, and immunological interactions. Gut microbiota dysbiosis, characterized by bacterial population alterations, contributes to intestinal homeostasis disruption and aberrant immune system activation, thereby exacerbating the inflammatory state. This study assesses the therapeutic efficacy of intraperitoneal (IP) injected flavonoids (apigenin, luteolin, and xanthohumol) in the reduction of inflammatory parameters and the modulation of the gut microbiota in a murine model of ulcerative colitis. Flavonoids interact with gut microbiota by modulating their composition and serving as substrates for the fermentation into other anti-inflammatory bioactive compounds. Our results demonstrate the effectiveness of luteolin and xanthohumol treatment in enhancing the relative abundance of anti-inflammatory microorganisms, thereby attenuating pro-inflammatory species. Moreover, all three flavonoids exhibit efficacy in the reduction of pro-inflammatory cytokine levels, with luteolin strongly demonstrating utility in alleviating associated physical UC symptoms. This suggests that this molecule is a potential alternative or co-therapy to conventional pharmacological interventions, potentially mitigating their adverse effects. A limited impact on microbiota is observed with apigenin, and this is attributed to its solubility constraints via the chosen administration route, resulting in its accumulation in the mesentery.

Methcathinone, a psychoactive substance with stimulant properties, has raised concerns in recent years due to its presence in urine screenings, even among individuals with no history of drug abuse. To prevent misjudgment, this work aims to explore the source of methcathinone in urine. A total of 58 urine samples tested positive for methcathinone in the National Taiwan University Hospital cohort, with 27 linked to illicit drug use and 31 from individuals with no drug use history. Co-occurrence analysis revealed a strong association between methcathinone and over-the-counter cold medications containing pseudoephedrine or ephedrine. In an in vivo experiment, participants who consumed pseudoephedrine-containing drugs showed the presence of methcathinone in their urine, suggesting a connection between these substances. Additionally, tests on pharmaceutical products containing pseudoephedrine detected small amounts of methcathinone as impurities. The findings suggest that the presence of methcathinone in nonillicit drug users may be attributed to impurities in over-the-counter pseudoephedrine-containing medications. This raises concerns about potential misinterpretations of drug screening results and underscores the need for more comprehensive criteria for assessing drug use. This study contributes to our understanding of the origin of methcathinone in urine, which has implications for legal justice and drug screening practices., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Sunscreen products constitute two distinct categories. Recreational sunscreens protect against high-intensity, episodic sun exposure, often applied over the entire body. In contrast, facial sunscreen products are designed for sub-erythemal, low-intensity daily sun exposure. Such different exposures necessitate distinctive product safety assessments. Building on earlier methods for predicting dermal disposition, a mechanistic model was developed to simulate plasma concentrations of seven organic sunscreen active ingredients: avobenzone, ensulizole, homosalate, octinoxate, octisalate, octocrylene, and oxybenzone, following facial application. In vitro permeation testing (IVPT) was performed with two different vehicles using a subset of the UV filters. These IVPT results, in addition to previously published IVPT data and published in vivo Maximal Usage Trial (MUsT) data for the UV filters, were used to train the mechanistic dermal model via a Bayesian Markov chain Monte Carlo (MCMC) method. An external validation of the trained model with real-world in vivo datasets demonstrated that the model's predicted UV filter plasma concentrations align well with experimental measurements and capture the observed inter-individual variability. Predictions of steady-state UV filter plasma concentrations under facial application scenarios at 5% concentration and at the maximal allowable concentrations were then generated by the trained model. Oxybenzone had the greatest predicted plasma concentration following facial application. Homosalate and octisalate predictions had high uncertainty associated with the absence of data. Several application scenarios pertaining to avobenzone, ensulizole, octocrylene and octinoxate were identified in which median plasma concentration levels were at 0.5 ng/ml or below when applied in the recreational or facial product. Model limitations include uncertainty in vehicle/water partitioning, formulation metamorphosis, and UV filter systemic clearance, all of which can be refined with additional data. For UV filters, limiting exposure to facial application reduces human safety concerns based on FDA established thresholds., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: J Frank Nash, John Troutman and Peter Styczynski are full time employees of The Procter & Gamble Company. Heidi Bialk is a full-time employee of Estee Lauder Company. Both companies are manufacturers of facial sunscreen products., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Strong Brønsted acids were found to catalyze the oxidative condensation of 2‐aminothiophenols with aryl alkyl ketones in DMSO to provide a wide range of complex 2‐arylbenzothiazines. With acetophenones, dimeric 2‐arylbenzothiazines were formed. On the other hand, the reaction with propiophenones resulted in 2:1 adducts whereas 1:1 adducts were produced with isobutyrophenones, benzoylacetonitrile and ethyl benzoylacetate. [ABSTRACT FROM AUTHOR]

NAC transcription factors (TFs) are one of the largest TF families in plants, and TaNACs have been known to participate in the regulation of the transcription of many yield-regulating genes in bread wheat. The TaCKX gene family members (GFMs) have already been shown to regulate yield-related traits, including grain mass and number, leaf senescence, and root growth. The genes encode cytokinin (CK) degrading enzymes (CKXs) and are specifically expressed in different parts of developing wheat plants. The aim of the study was to identify and characterize TaNACs involved in the cis -regulation of TaCKX GFMs. After analysis of the initial transcription factor data in 1.5 Kb cis -regulatory sequences of a total of 35 homologues of TaCKX GFMs, we selected five of them, namely TaCKX1-3A , TaCKX22.1-3B , TaCKX5-3D , TaCKX9-1B , and TaCKX10 , and identified five TaNAC genes: TaNACJ-1 , TaNAC13a , TaNAC94 , TaNACBr-1 , and TaNAC6D , which are potentially involved in the cis -regulation of selected TaCKX genes, respectively. Protein feature analysis revealed that all of the selected TaNACs have a conserved NAC domain and showed a stable tertiary structure model. The expression profile of the selected TaNACs was studied in 5 day-old seedling roots, 5-6 cm inflorescences, 0, 4, 7, and 14 days-after-pollination (DAP) spikes, and the accompanying flag leaves. The expression pattern showed that all of the selected TaNACs were preferentially expressed in seedling roots, 7 and 14 DAP spikes, and flag leaves compared to 5-6 cm inflorescence and 0 and 4 DAP spikes and flag leaves in Kontesa and Ostka spring wheat cultivars (cvs.). In conclusion, the results of this study highlight the potential role of the selected TaNACs in the regulation of grain productivity, leaf senescence, root growth, and response to various stresses.

Background: Dyclonine hydrochloride mucilage is a topical anaesthetic formulated for mucosal surfaces. It is employed frequently for topical anaesthesia of the pharynx prior to endoscopic examinations such as electronic gastroscopy, and few adverse reactions have been reported. This article describes a patient who experienced a transient but severe disturbance of consciousness following oral dyclonine hydrochloride mucilage administration., Case Presentation: A 75-year-old female presenting with gastrointestinal bleeding was examined by electronic gastroscopy. Six minutes after oral dyclonine hydrochloride mucilage administration, the patient entered a comatose-like state accompanied by loss of limb muscle tone and profuse perspiration. This response was not accompanied by changes in cardiac rhythm, blood pressure, or respiration rate, suggesting an effect on higher brain centres. After ten minutes, the patient's symptoms were alleviated., Conclusion: We suggest that sites of dyclonine hydrochloride mucilage use be equipped with appropriate rescue devices for these rare events., (© 2024. The Author(s).)

Flopropione (Flo) has been used for gallstone and urolithiasis as a spasmolytic agent almost exclusively in Japan. According to the package insert, its main mechanism is catechol-O-methyltransferase (COMT) inhibition and anti-serotonergic effect. This is obviously contrary to pharmacological common sense, but it is described that way in pharmacology textbooks and occurs in questions in the National Examination for Pharmacists in Japan. As this is a serious problem in education, we re-examined the action of Flo. The guinea pig ureter was hardly contracted by serotonin, but noradrenaline (NA) elicited repetitive twitch contraction, which was inhibited by Flo. The sphincter of Oddi (SO) exhibited a spontaneous repetitive twitch contraction, which was inhibited by NA and Flo. The inhibitory effect of NA was reversed by α- and β-blockers, whereas that of Flo was not. Entacapone, a representative COMT inhibitor, did not affect the movement of the ureter and the SO. Nifedipine suppressed carbachol-induced contraction of the taenia coli, spontaneous movement of the SO, and NA-induced contraction of the ureter to almost the same extent, whereas Flo did not inhibit the taenia coli, but inhibited the contraction of the SO and the ureter. The inhibitory pattern of Flo resembled that of the ryanodine receptor agonist 4-chloro-m-cresol and the inositol 1,4,5-trisphosphate (IP 3 ) receptor antagonist 2-aminoethoxydiphenyl borate. It is concluded that COMT inhibition or serotonin inhibition is not involved in the spasmolytic action of Flo. Flo might act on ryanodine receptors and/or IP 3 receptors, which are responsible for periodic Ca release from Ca stores, to disrupt coordinated Ca dynamics.

Background: Selected natural compounds exhibit very good antiviral properties. Especially, the medicinal plant Humulus lupulus (hop) contains several secondary plant metabolites some of which have previously shown antiviral activities. Among them, the prenylated chalcone xanthohumol (XN) demonstrated to be a potent inhibitor of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (M pro )., Hypothesis/purpose: Following the finding that xanthohumol (XN) is a potent inhibitor of SARS-CoV-2 M pro , the effect of XN and its major derivatives isoxanthohumol (IXN), 6-prenylnaringenin (6-PN), and 8-prenylnaringenin (8-PN) from hops on SARS-CoV-2 papain-like protease (PL pro ) were investigated., Study Design: The modulatory effect of the hop compounds on PL pro were studied first in silico and then in vitro. In addition, the actual effect of hop compounds on the replication of SARS-CoV-2 in host cells was investigated., Methods: In silico docking analysis was used to predict the binding affinity of hop compounds to the active site of PL pro . A recombinant PL pro was cloned, purified, characterized, and analyzed by small-angle X-ray scattering (SAXS), deISGylation assays, and kinetic analyses. Antiviral activity of hop compounds was assessed using the fluorescently labeled wildtype SARS-CoV-2 (icSARS-CoV-2-mNG) in Caco-2 host cells., Results: Our in silico docking suggests that the purified hop compounds bind to the active site of SARS-CoV-2 PL pro blocking the access of its natural substrates. The hop-derived compounds inhibit SARS-CoV-2 PL pro with half maximal inhibitory concentration (IC 50 ) values in the range of 59-162 µM. Furthermore, we demonstrate that XN and 6-PN, in particular, impede viral replication with IC 50 values of 3.3 µM and 7.3 µM, respectively., Conclusion: In addition to the already known inhibition of M pro by XN, our results show, for the first time, that hop-derived compounds target also SARS-CoV-2 PL pro which is a promising therapeutic target as it contributes to both viral replication and modulation of the immune system. These findings support the possibility to develop new hop-derived antiviral drugs targeting human coronaviruses., Competing Interests: Declaration of Competing Interest The funders had no role in the collection, analysis, or interpretation of data, in writing of the manuscript, or in the decision to publish the results. The University Hospital of Tübingen is assignee for the following patents (US-9855242-B2, EP2968261A1) concerning the use of hop compounds for an immunomodulation. All authors declare that apart from the above points there are no other conflicts of interest., (Copyright © 2023. Published by Elsevier GmbH.)

Xanthohumol (XN), a polyphenol found in the hop plant ( Humulus lupulus ), has antioxidant, anti-inflammatory, prebiotic, and anti-hyperlipidemic activity. Preclinical evidence suggests the gut microbiome is essential in mediating these bioactivities; however, relatively little is known about XN's impact on human gut microbiota in vivo . We conducted a randomized, triple-blinded, placebo-controlled clinical trial (ClinicalTrials.gov NCT03735420) to determine safety and tolerability of XN in healthy adults. Thirty healthy participants were randomized to 24 mg/day XN or placebo for 8 weeks. As secondary outcomes, quantification of bacterial metabolites and 16S rRNA gene sequencing were utilized to explore the relationships between XN supplementation, gut microbiota, and biomarkers of gut health. Although XN did not significantly change gut microbiota composition, it did re-shape individual taxa in an enterotype-dependent manner. High levels of inter-individual variation in metabolic profiles and bioavailability of XN metabolites were observed. Moreover, reductions in microbiota-derived bile acid metabolism were observed, which were specific to Prevotella and Ruminococcus enterotypes. These results suggest interactions between XN and gut microbiota in healthy adults are highly inter-individualized and potentially indicate that XN elicits effects on gut health in an enterotype-dependent manner.

As a part of our continuing exploration to discover new potential promising fungicide candidates, eighteen sulfonate derivatives (3a-3r) containing a kakuol moiety were designed and synthesized. Synthetic sulfonate derivatives were tested comprehensively for antifungal activities against four plant pathogenic fungi (Botrytis (B.) cinerea, Valsa (V.) mali, Fusarium (F.) graminearum, Sclerotinia (S.) sclerotiorum), and their structure activity relationships were summarized. Especially, derivatives 3i and 3j exhibited remarkable activity against V. mali, with the inhibition rates of 99.8 and 100%, which were slightly superior to that of carbendazim (98.9%), a reference fungicide. Moreover, derivatives 3a, 3k and 3q possess the broader antifungal spectrum against three tested plant pathogenic fungi with inhibition rates over 60%. Structure-activity relationship (SAR) analysis indicated that the introduction of 2-F or 3-F into the benzene ring would give rise to a remarkable increase of the antifungal activity against V. mali.

Catalytic asymmetric direct-type aldol reactions of ketones with aldehydes are a perennial puzzle for organic chemists. Notwithstanding the emergence of a myriad of chiral catalysts to address the inherent reversibility of the aldol products, a general method to access acyclic α-chiral ketones from prochiral aryl ketones has remained an unmet synthetic challenge. The approach outlined herein is fundamentally different to that used in conventional catalysis, which typically commences with an α-proton abstraction by a Brønsted base. The use of a chiral 2,2'-bipyridine scandium complex enabled the hydroxymethylation of propiophenone to be run under base-free conditions, which avails effectual suppression of hydrolytic deactivation of the Lewis acid catalyst. Intriguingly, the use of water as a reaction medium had an overriding effect on the progress of the reaction. The sagacious selection of sodium dodecyl sulfate and lithium dodecyl sulfate as surfactants allowed a variety of propiophenone derivatives to react in a highly enantioselective manner.

Aims: To describe National Diabetes Prevention Program (NDPP) uptake, retention, and outcomes by enrollee characteristics and program type., Methods: We studied 776 adult University of Michigan employees, dependents, and retirees with prediabetes and overweight or obesity who enrolled in one of four CDC-recognized NDPPs at no out-of-pocket cost. Programs included 1) an in-person classroom-based program led by certified diabetes educators in an endocrinology outpatient clinic; 2) an in-person classroom-based program led by trained peer instructors in community settings; 3) an in-person fitness-focused program led by trained lifestyle coaches; and 4) an online digital program led by personal health coaches with virtual group meetings. Data from the insurer and surveys were analyzed., Results: Older individuals with hypertension and cardiovascular disease were more likely to enroll in classroom-based programs. Program time, location, and perceived focus on diet or physical activity influenced program selection. Retention, weight loss, and physical activity were greater among enrollees in in-person classroom-based programs. Changes in blood pressure, lipid levels, self-rated health, and health-related quality-of-life did not differ by program, nor did Type 2 diabetes mellitus incidence., Conclusions: Individuals with prediabetes who enrolled in a NDPP achieved health benefits regardless of the type of program they chose., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

For many precision devices with limited amount of lubricants, the retention of lubricating oil between solid surfaces is of great significance for the lubrication reliability in the long-term operation. In this study, the spreading behavior of a synthetic 1,3-diketone lubricant (1-(4-ethyl phenyl) nonane-1,3-dione) 02/06 on steel surfaces was investigated. By measuring the surface tension of oil and the surface energy of steel, the spreading parameter of 02/06 was determined, which was much smaller than the reference oils with similar viscosity. Rotary friction test shows that 02/06 was positioned at the contact region in the presence of a strong centrifugal force and performed a stable ultralow friction. Moreover, the addition of 02/06 into the reference oils also improved the lubricant retention. [ABSTRACT FROM AUTHOR]

Two practical and efficient approaches have been implemented as alternative procedures for the synthesis of naftifine and novel diversely substituted analogues 16 and 20 in good to excellent yields, mediated by Mannich-type reactions as the key step of the processes. In these approaches, the y-aminoalcohols 15 and 19 were obtained as the key intermediates and their subsequent dehydration catalyzed either by Br0nsted acids like H2SO4 and HCl or Lewis acid like AlCl3, respectively, led to naftifine, along with the target allylamines 16 and 20. The antifungal assay results showed that intermediates 18 (bearing both a β-aminoketo- and N-methyl functionalities in their structures) and products 20 were the most active. Particularly, structures 18b, 18c, and the allylamine 20c showed the lowest MIC values, in the 0.5-7.8 µg/mL range, against the dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes. Interesting enough, compound 18b bearing a 4-Br as the substituent of the phenyl ring, also displayed high activity against Candida albicans and Cryptococcus neoformans with MIC80 = 7.8 µg/mL, being fungicide rather than fungistatic with a relevant MFC value = 15.6 µg/mL against C. neoformans. [ABSTRACT FROM AUTHOR]

This paper aims to observe the therapeutic effect of butylphthalide sodium chloride injection combined with urokinase in the treatment of acute ischemic stroke. A total of 60 patients with acute ischemic stroke were randomly divided into 2 groups: combined treatment group (butylphthalide sodium chloride injection + urokinase, N = 30) and control group (urokinase only, N = 30). National Institute of Health Stroke Scale (NIHSS) and Barthel Index (BI) were used to evaluate the improvement of neurological function and curative effect. Adverse reactions were also observed. As results, the markedly effective rate was 36.67% (11/30) and the total efficiency rate was 93.33% (28/30) in combined treatment group, while they were 10% (3/30) and 56.67% (17/30) in control group. There was significant difference between 2 groups ( χ2 = 13.195, P = 0.004). Besides, the neurological function of patients in 2 groups elevated to different degrees at each time point after treatment (P = 0.020). There was no significant difference in the incidence rate of adverse reactions between 2 groups (P = 0.572). The results indicated that the curative effect of butylphthalide sodium chloride injection combined with urokinase in the treatment of acute ischemic stroke is better than that of urokinase. doi: 10.3969/j.issn.1672-6731.2014.09.013

Irgacure 907 (2-Methyl-4′-(methylthio)-2-morpholinopropiophenone) is a highly efficient photoinitiator which undergoes standard Norrish Type I photocleavage. It is widely used to initiate the photopolymerization of chemically unsaturated prepolymers. In this work, the photocleavage reaction mechanisms, as well as excited state properties and the underlying relaxation mechanisms upon photoexcitation of Irgacure 907, are studied using DFT calculations. To investigate the mechanisms, the excited singlet and triplet states have considered in detail. Our calculations indicate that the radical formation for Irgacure 907 originates from the triplet states, which is typical Type-I photoinitiators. Upon irradiation, it will undergo a α-cleavage process to form two radical species. In line with the Jablonski-Type diagram, the ground state of Irgacure 907 excites to a higher state, which is characterized by ππ* singlet state (S 2 ), followed by an internal conversion (IC) to the first excited state (S 1 ). The subsequent intersystem crossing (ISC) can occur between S 1 and triplet state that has nπ* character. As expected, after excitation, the photoinitiator undergoes rapid intersystem crossing (ISC) which is an important step in the photochemical process. [ABSTRACT FROM AUTHOR]

The objective of present work was to develop and validate a simple, accurate, rapid and precise stability indicating HPTLC method for simultaneous estimation of Eperisone hydrochloride (EPE) and Diclofenac sodium (DICLO) in bulk and in capsule dosage form. The method employed Merck TLC plates precoated with Silica F254. After several trials, ethyl acetate: methanol (8:2, v/v), was chosen as the mobile phase with saturation time 15 min, which showed good resolution and acceptable peak parameters. The densitometric analysis of both drugs was carried out at 266 nm. The linearity coefficient was found to be 0.999 for Eperisone hydrochloride (EPE) and 0.999 for Diclofenac sodium (DICLO). The Rf values were found to be 0.38 ± 0.02 and 0.73 ± 0.03 for EPE and DICLO. Stability study of EPE and DICLO was carried out by Forced degradation study. The developed method was successfully applied to estimate the amount of Eperisone hydrochloride and Diclofenac sodium in bulk and capsule dosage form. [ABSTRACT FROM AUTHOR]

Xanthohumol (XN) has numerous compelling physiological activities, but the poor solubility and stability severely limit its utilization. Therefore, a microemulsion (ME) delivery system based on biosurfactant sophorolipids (SLs) was established and its improvement on physicochemical properties of XN was investigated. The results showed that the systems increased the solubility of XN by about 4000 times, and its half-life during storage was extended to over 150 days. Partial replacement of Tween 80 with SL did not greatly affect their ability to form O/W subregions (in the high aqueous phase), but further improved the solubilization efficiency, storage stability, and antioxidant properties of XN. In vitro models revealed the release profile of XN from the systems followed non-Fickian diffusion, and the ME structure markedly strengthened its digestive stability and bioaccessibility. These results indicated that SL-based ME systems had great potential as a green solubilization and delivery method for XN and other hydrophobic drugs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

An unknown impurity was detected in in-house prepared ephedrine hydrochloride (HCl) 5 mg/mL prefilled sterilized syringes when applying a stability-indicating British Pharmacopoeia 2018 impurity method for ephedrine injection. Ultraviolet, chromatographic, mass spectral, and physicochemical methods were combined to identify the unknown impurity. The unknown impurity was identified as methcathinone, which is generated from ephedrine drug substance through an oxidation reaction. A formulation study, in which different process adjustments were tested, was carried out to reduce the amount of unknown impurity. Nitrogen gassing in combination with 0.05 M citrate buffer addition proved to be the most potent process adjustment in reducing methcathinone formation in ephedrine HCl 5 mg/mL prefilled sterilized syringes after 4 months of storage in the dark at room temperature (20 °C ± 5 °C). More detailed research on the long-term stability of the reformulated ephedrine HCl drug product is currently underway, with promising results for up to 9 months gathered already., (© 2023. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Methaemoglobin (MetHb) forming compounds such as para-aminopropiophenone (PAPP) and sodium nitrite (NaNO2) have recently been adopted for the lethal control of a range of invasive carnivores and mustelids. Determining the relative hazard of these compounds to non-target bird species is an important component of ecological risks evaluation. Problematically, some potential non-target bird species may be as small as 10 g in body mass, thus placing limitations on blood volumes that can be routinely sampled. Accordingly, we developed methods to quantify markers of increasing methaemoglobinaemia at their point of collection that required only 5 μL of whole blood. A 3 μL blood aliquot is pipetted into a plastic micro-cuvette and placed in a custom made holder optically coupled to the Ocean Optics spectrometer, enabling absorbance for oxyhaemoglobin (HbO: 575 nm) and MetHb (630 nm) to be determined. Haemoglobin (HbFe2+), packed cell volume (PCV) and lactate (LAC) data were generated from the remaining 2 μL aliquot apportioned to biosensor strips for the Cera-Check® and Lactate Scout® point-of-care devices. After oral doses of PAPP, a methaemoglobinaemia absorbance index (MAI = absorbance 575 nm-absorbance 630 nm) was strongly and significantly associated with dose-dependent declines in HbFe2+ in 9 bird species. Quantifying dose-dependent responses to MetHb-forming agents at the point of sample collection avoids analytical and storage artifacts arising from sample degradation that appears to be a much greater problem in avian blood compared to mammalian blood., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Marks et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Xanthohumol, a chalcone unique to hops, has attracted attention from researchers due to its several pharmacological effects on humans. In industry, hops are almost exclusively used in beer production, generating tons of solid waste - hot trub from the boiling step and spent hops from the dry hopping - rich in biocompounds, among them xanthohumol, that could be recovered and used for several nutritional purposes. The literature is extensive on extraction processes of xanthohumol directly from hops, but only a few studies present its recovery from brewery solid waste. We focus on presenting the xanthohumol characteristics and benefits for human consumption, and discuss the main extraction techniques, their advantages and limitations, to prospect strategies to recover this high-value compound from brewing solid waste. Recent extraction processes represent promising approaches to overcome the limitations of conventional methods, but further studies are still needed to understand xanthohumol extraction and purification and induce industrial upscaling., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

A metal-free nitration of the α-C-H to carbonyl in propiophenones was achieved with I2/NaNO2 in the presence of an oxidant in dimethyl sulfoxide (DMSO) as the medium. Conversely under similar conditions, reaction of acetophenones produced thiohydroximic acids via a radical-based cascade event which involves oxidative nitration of the α-carbon to a carbonyl followed by Michael addition of the thiomethyl group from DMSO and subsequent rearrangement. Besides DMSO, the scope of the reaction encompasses other symmetrical and unsymmetrical dialkylsulfoxides. [ABSTRACT FROM AUTHOR]

A series of rate studies were conducted to evaluate the steric and electronic properties that govern the reactivity of iodoarene amide catalysts in the α-oxytosylation of propiophenone. A meta-substituted benzamide catalyst emerged as the most reactive. This catalyst was employed in the α-oxytosylation of a series of substituted propiophenones, returning the α-tosyloxy ketone products in excellent isolated yield. [ABSTRACT FROM AUTHOR]

New series of enantiopure 3,3'-diiodobinaphthol- and 3,3'- diiodobiphenol-based molecules have been synthesized and used as chiral hypervalent iodine oxidation organocatalysts in the α-oxytosylation of propiophenone. When we compared these new organocatalysts to our previous series of 3,3'-diiodo-1,1'-binaphthalene-2,2'-diol-fused maleimides, we have made two important observations: the maleimide moiety is the best moiety for obtaining moderate enantioselectivities, and the presence of an aliphatic substituent on the biaryl part of the catalyst enhances the enantioselectivity. [ABSTRACT FROM AUTHOR]

In this study, alcohol dehydrogenase (EC 1.1.1.2) from Lactobacillus brevis and glycerol dehydrogenase (EC 1.1.1.6) from Cellulomonas sp. were used for the reduction of ( S )-2-hydroxypropiophenone to (1 S , 2 S )- and (1 R , 2 S )-1-phenylpropane-1,2-diol, respectively. As both dehydrogenases belong to NADH-dependent oxidoreductases, due to high coenzyme cost, the possibility of NADH regeneration was considered by using the enzyme-coupled regeneration system with formate dehydrogenase (EC 1.2.1.2) from Candida boidinii . All three enzymes were kinetically characterized and the kinetics of all reactions were determined using the method of initial rates. Based on kinetic results mathematical models were developed for the synthesis of both phenylpropane 1,2-diols for the systems with and without coenzyme regeneration and were validated in a batch reactor. The equilibrium conversions of 60% and 33% were achieved without coenzyme regeneration using alcohol and glycerol dehydrogenase, respectively, while with coenzyme regeneration a complete ( S )-2-hydroxypropiophenone conversion was achieved with both enzymes. [ABSTRACT FROM AUTHOR]

A general and efficient method for the synthesis of 1-substituted 3-amino-1 H -1,2,4-triazoles has been developed. The desired 3-amino-1 H -1,2,4-triazoles ( 3 ) were prepared in good to excellent yields from ethyl N -(5-phenyl-1,2,4-oxadiazol-3-yl)formimidate ( 1a ) and anilines or amines ( 2 ) via a one-pot process involving formimidamide formation followed by a thermal monocyclic rearrangement. The benzoyl protecting group could be readily removed by sulfuric acid promoted deprotection. [ABSTRACT FROM AUTHOR]

1-(4-Substituted phenyl)-2-phenylethanones were aminomethylated with paraformaldehyde and amine in ethanol to produce α-phenyl-β-amino-4-substituted propiophenones. Interaction of these with Grignard reagents in ether yielded tertiary aminopropan-1-ols and their hydrochlorides. Quite efficient inhibition, at differing levels, of adenosine deaminase (ADA, E.C. 3.5.44), one of the key enzymes in purine metabolism, by the compounds synthesized here was demonstrated. A structure-activity relationship was found for ADA inhibition. Most of the compounds synthesized here were found to lack antibacterial activity; only compounds Va, Vd, and VId displayed moderate levels of antibacterial activity against Gram-positive microorganisms. [ABSTRACT FROM AUTHOR]

A sensitive liquid chromatography–electrospray ionization-ion trap mass spectrometry (LC–ESI-ITMS) method was utilized for the simultaneous analysis of four designer drugs and their in vitro metabolites in rat liver microsome S 9 fraction. Four designer drugs, including methcathinone (MC), 3,4-methylenedioxymethcathinone (MDMC), 3,4-methylenedioxy-pyrovalerone (MDPV) and 4′-methyl-α-pyrrolidinopropiophenone (MPPP), were individually incubated with rat liver microsome S 9 fraction, and the incubation mixtures were pooled together and analyzed by LC–ESI-ITMS simultaneously. Besides four designer drugs, five of their main metabolites were identified via the analysis of protonated molecules and tandem mass spectrometry data. Meanwhile, the quantification analysis of four designer drugs in rat liver microsome S 9 fraction was performed, the calibration curves showed good linearity in the range of 0.01–5.0 μg/mL and the detection limits were below 0.03 μg/mL with RSDs less than 5.9% and recovery ratios above 77.4%. The experimental results not only showed that these designer drugs could be easily metabolized in rat liver microsome, and also displayed the superiorities of the method including time and cost saving, high efficiency, sensitivity and selectivity. The studies in this study indicated that the approach could be applied in the determination of illicit drugs and their metabolites in medical, pharmaceutical and forensic investigations. [ABSTRACT FROM AUTHOR]

A new organic salt of dyclonine (DYC) with p-toluenesulfonic acid ( p-TSA) has been synthesized and characterized by elemental analysis, single-crystal X-ray diffraction, IR spectra, UV spectra, and hot stage microscopy. The structure determination shows that the asymmetric unit of the salt consisting of two entire ions of DYC and p-TSA, and that they are not symmetric. The salt is primarily stabilized by a strong N-H···O hydrogen bonding interaction between DYC and p-TSA. In addition, the luminescent properties and biological activities are discussed. [ABSTRACT FROM AUTHOR]

A metal-free protocol for the α-benzoxylation of ketones has been developed by using terminal aryl alkenes as an arylcarboxy surrogate. Moderate to good yields were attained for a variety of propiophenones and acetophenones by using tetra- n-butylammonium iodide (TBAI) as the catalyst and tert-butyl hydroperoxide (TBHP) as the oxidant under ambient reaction conditions. [ABSTRACT FROM AUTHOR]

A novel copper-catalyzed direct α-ketoesterification of propiophenones with acetophenones via C(sp3)–H oxidative cross-coupling was developed. The reaction utilized O2 as a clean oxidant with high atom economy and the starting materials are facile and commercially available. [ABSTRACT FROM AUTHOR]

The selenoprotein thioredoxin reductases(TrxRs) are attractivetargets for anticancer drugs development. Xanthohumol (Xn), a naturallyoccurring polyphenol chalcone from hops, has received increasing attentionbecause of its multiple pharmacological activities. We synthesizedXn and its 43 analogues and discovered that compound 13ndisplayed the highest cytotoxicity toward HeLa cells (IC50= 1.4 μM). Structure–activity relationship study indicatesthat the prenyl group is not necessary for cytotoxicity, and introducingelectron-withdrawing group, especially on the meta-position, is favored.In addition, methylation of the phenoxyl groups generally improvesthe potency. Mechanistic study revealed that 13nselectivelyinhibits TrxR and induces reactive oxygen species and apoptosis inHeLa cells. Cells overexpressing TrxR are resistant to 13ninsult, while knockdown of TrxR sensitizes cells to 13ntreatment, highlighting the physiological significance of targetingTrxR by 13n. The clarification of the structural determinantsfor the potency would guide the design of novel potent molecules forfuture development. [ABSTRACT FROM AUTHOR]

Fish skin collagen films are widely used as adhesives in medicine and cosmetology. Ultraviolet (UV) irradiation can be considered as an effective sterilization method for biomaterials, however, it may also lead to material photodegradation. In this work, the influence of xanthohumol and propanediol on the physico-chemical properties of collagen films before and after UV irradiation was studied. Collagen for this research was extracted from silver carp skin and thin films were fabricated by the solution casting methods. The structure of films was researched using infrared spectroscopy. The surface properties of films were investigated using Atomic Force Microscopy (AFM) and contact angle measurements. Mechanical properties were measured as well. It was found that the addition of xanthohumol and propanediol modified the roughness of collagen films and their mechanical properties. UV irradiation led to the water loss from the film and modification of the collagen structure. In the presence of propanediol and xanthohumol the water loss after UV irradiation was smaller than in UV-irradiated collagen films without these additives., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Biotransformation of 3-chloro-1-phenylpropan-1-one 1 in sixteen selected cultures of yeast strains has been carried out. For most of the biocatalysts studied the substrate was fully consumed after 1–9 h of transformation, with the exception of the culture of Saccharomyces brasiliensis KCh 905, in which after 24 h trace amounts of the substrate were still visible (2%). However, apart from the expected enantiospecific reduction of the substrate to 3-chloro-1-phenylpropan-1-ol 3 , the main biotransformation products comprised of a dehalogenation product—propiophenone 2 and the product of its reduction—1-phenylpropan-1-ol 4 . It was only in the cultures of five strains: Saccharomyces brasiliensis KCh 905, Rhodotorula marina KCh 77, Candida parapsilosis KCh 909, Candida viswanathii KCh 120, and Saccharomyces cerevisiae KCh 464 that 3-chloro-1-phenylpropan-1-ol 3 was observed in amounts of more than 10% of the product mixture. ( S )-3-Chloro-1-phenylpropan-1-ol with ee = 91% was identified after 9 h of biotransformation in the culture of Candida viswanathii KCh 120, whereas ( R )-3-chloro-1-phenylpropan-1-ol with ee = 28% was found in the culture of Aphanocladium album KCh 417. 1-Day biotransformation of propiophenone 2 in the cultures of Rhodotorula strains gave ( S )-1-phenylpropan-1-ol 4 with a very high ee (95–99%) and 85–99% of substrate conversion, whereas transformation of this substrate in the cultures of Candida viswanathii KCh 120 and Candida parapsilosis KCh 909 led to ( R )-1-phenylpropan-1-ol with ee = 98% and 97%, respectively. During biotransformation of propiophenone the percent composition of the reaction mixtures changed with time. Employment of the racemic mixture of 1-phenylpropan-1-ol 4 as a substrate for biotransformations allowed us to observe that the biocatalysts tested were capable of enantioselective oxidation of ( S )-1-phenylpropan-1-ol. An exception was the culture of Rhodotorula glutinis KCh 242, in which after one day of biotransformation ( S )-1-phenylpropan-1-ol was obtained with ee = 96%. [ABSTRACT FROM AUTHOR]

This paper aims to observe the therapeutic effect of butylphthalide sodium chloride injection combined with urokinase in the treatment of acute ischemic stroke. A total of 60 patients with acute ischemic stroke were randomly divided into 2 groups: combined treatment group (butylphthalide sodium chloride injection + urokinase, N = 30) and control group (urokinase only, N = 30). National Institute of Health Stroke Scale (NIHSS) and Barthel Index (BI) were used to evaluate the improvement of neurological function and curative effect. Adverse reactions were also observed. As results, the markedly effective rate was 36.67% (11/30) and the total efficiency rate was 93.33% (28/30) in combined treatment group, while they were 10% (3/30) and 56.67% (17/30) in control group. There was significant difference between 2 groups (χ2 = 13.195, P = 0.004). Besides, the neurological function of patients in 2 groups elevated to different degrees at each time point after treatment (P = 0.020). There was no significant difference in the incidence rate of adverse reactions between 2 groups (P = 0.572). The results indicated that the curative effect of butylphthalide sodium chloride injection combined with urokinase in the treatment of acute ischemic stroke is better than that of urokinase. [ABSTRACT FROM AUTHOR]

Abstract: A Schiff base, 2-hydroxy-benzoic acid [1-(2-hydroxy-phenyl)-propylidene]-hydrazide (H2hbpp) and its Mn(II), Cu(II) and Zn(II) complexes have been synthesized. These compounds have been characterized by different physico-chemical and spectroscopic techniques (UV–Vis, IR, NMR and ESI-Mass). The molecular structure of H2hbpp and its Mn(II) and Zn(II) complexes are determined by single crystal X-ray diffraction technique. In Mn(II) and Cu(II) complexes, the ligand coordinates through azomethine-N, carbonyl-O and phenolate-O (2-hydroxypropiophenone) forming a mono-nuclear 6-coordinate distorted octahedral geometry around metal. However, Zn(II) complex forms a phenoxo-bridged centrosymmetric dimer with 5-coordinate distorted square pyramid geometry around each metal ion. In this complex, the ligand bonds through azomethine-N, carbonylate-O and two phenolate-O, and a DMSO molecule occupies one of the vacant site of each metal. The structure of Cu(II) complex has been satisfactorily modeled by density functional theory (DFT) and time dependent-DFT (TD-DFT) calculations. The corrosion inhibition study of the synthesized compounds for mild steel in 1M HCl medium has also been performed and the activity is found in the order: H2hbpp