Propionic Acid Derivatives Research Articles

Mesoporous TiO2/Celite‐Supported Hydrolysis/Decarboxylation of Benzyl Meldrum's Acid Derivatives: Application to the Synthesis of Hydrocinnamic Acid Derivatives

AbstractThis study describes a method for transforming benzyl Meldrum's acid (BMA) derivatives into aryl propionic acid (hydrocinnamic acid) derivatives using TiO2 P25 or Celite surfaces under mild conditions. This selective decarboxylation and hydrolysis process is particularly effective for enolizable Meldrum's acid derivatives. A key feature of this transformation is its chemooselectivity, particularly with acetylated BMA derivatives, which yield the corresponding aryl propionic acids. The method offers several advantages, including compatibility with a wide range of structurally diverse aryl propionic acids, reliance on inexpensive materials, elimination of bases and neutralizing agents, and a simplified work‐up procedure.

Discovery of Propionic Acid Derivatives with a 5-THIQ Core as Potent and Orally Bioavailable Keap1-Nrf2 Protein-Protein Interaction Inhibitors for Acute Kidney Injury.

Keap1 plays a crucial role in regulating the Nrf2-mediated cytoprotective response and is increasingly targeted for oxidative stress-related diseases. Using small molecules to disrupt the Keap1-Nrf2 protein-protein interaction (PPI) has emerged as a new strategy for developing Nrf2 activators. Through extensive structure-activity relationship studies, we identified compound 56, which features a unique 5-tetrahydroisoquinoline scaffold and acts as a potent inhibitor of the Keap1-Nrf2 PPI. Compound 56 exhibited significant inhibitory activity (IC50 = 16.0 nM) and tight Keap1 binding affinity (Kd = 3.07 nM), along with acceptable oral bioavailability (F = 20%). Notably, 56 enhanced antioxidant defenses in HK-2 renal tubular epithelial cells and significantly reduced plasma creatinine and blood urea nitrogen levels in acute kidney injury (AKI) mice. These findings collectively position compound 56 as a promising candidate for the treatment of AKI.

Steroidal Anti-Inflammatory Drugs for Oral Surgery: A Systematic Review and Meta-Analysis.

The aim of the present study was to investigate if there are differences in mitigation acute pain following oral surgery procedures within a hospital setting and regarding various medication regimens. A systematic literature search was performed between the years 2013 and 2023, including the databases PUBMED, Cochrane and Scopus, to identify the clinical trials investigating the prescription of non-steroidal (NSAID's) anti-inflammatory drugs before or after an oral surgery. A meta-analysis with meta-regression model was employed on the primary and secondary outcomes, such as pain, swelling and trismus. Thirty-six articles were included, 6 of them being retrospective and 30 prospective, with a higher proportion of women than men, at a ratio of 1.34:1 and an average age of 31.9 years. Drugs with medium duration of action demonstrated lower values for pain and swelling. Regarding these parameters, pain and swelling, propionic acid derivatives and acetic acid derivatives exhibited lower values respectively. The quality of evidence was low to very low- certainty. The meta-analysis suggests that postoperative pain, swelling and trismus following oral surgery management may be effectively treated with the following drugs: NSAID medium-duration action drugs; propionic acid derivatives for lower pain levels and acetic acid derivatives for lower swelling measures; and Ibuprofen 400mg every 8h for 3 days or less. Anti-inflammatory and analgesic drugs are prescribed to prevent or treat dental pain. Ibuprofen 400mg was the most prescribed drug after or before an oral surgery procedure. However, the evidence is indirect and needs to be interpreted with caution.

NSAIDs, analgesics, antiplatelet drugs, and decline in renal function: a retrospective case-control study with SIDIAP database

IntroductionWe aim to explore the association between NSAIDs consumption, Symptomatic Slow Action Drugs for Osteoarthritis (SYSADOA), analgesics, and antiplatelet drugs, and decline in renal function by estimated Glomerular Filtration Rate (eGFR).MethodsWe performed a case-control study using the SIDIAP database in Catalonia. We considered defined cases, patients with an eGFR value ≤ 45 ml/min/1.73 m2 in the period 2010–2015 with a previous eGFR value ≥ 60, and no eGFR ≥ 60 after this period. Controls had an eGFR ≥ 60 with no previous eGFR < 60. Five controls were selected for each case, matched by sex, age, index date, Diabetes Mellitus and Hypertension. We estimated Odds Ratios (OR, 95% Confidence Intervals) of decline in renal function for drugs group adjusting with logistic regression models, by consumption measured in DDD. There were n = 18,905 cases and n = 94,456 controls. The mean age was 77 years, 59% were women. The multivariate adjusted model showed a low risk for eGFR decline for NSAIDs (0.92;0.88–0.97), SYSADOA (0.87;0.83–0.91) and acetaminophen (0.84;0.79–0.89), and an high risk for metamizole (1.07;1.03–1.12), and antiplatelet drugs (1.07;1.03–1.11). The low risk in NSAIDs was limited to propionic acid derivatives (0.92;0.88–0.96), whereas an high risk was observed for high doses in both acetic acid derivatives (1.09;1.03–1.15) and Coxibs (1.19;1.08–1.30). Medium and high use of major opioids shows a high risk (1.15;1.03–1.29). Triflusal showed high risk at medium (1.23;1.02–1.48) and high use (1.68;1.40–2.01).ConclusionWe observed a decline in renal function associated with metamizole and antiplatelet agent, especially triflusal, and with high use of acetic acid derivates, Coxibs, and major opioids. Further studies are necessary to confirm these results.

Cross-hypersensitivity reactions to non-steroidal anti-inflammatory drugs, manifested as urticaria and/or angioedema, anaphylaxis

BACKGROUND: The main mechanism of drug hypersensitivity to non-steroidal anti-inflammatory drugs is associated with inhibition of cyclooxygenase type 1, which leads to cross-hypersensitivity reactions to non-steroidal anti-inflammatory drugs from various subgroups of different chemical structures. Clinically, cross-hypersensitivity usually manifests in the form of urticaria and/or angioedema. AIM: To characterize a group of patients with cross-hypersensitivity to non-steroidal anti-inflammatory drugs manifesting as urticaria / angioedema / anaphylaxis. MATERIALS AND METHODS: To achieve this aim a prospective single-center study was conducted. Patients with a presumptive diagnosis of drug hypersensitivity to non-steroidal anti-inflammatory drugs (n=307) were consulted. A group of patients (n=237) with high probability of such reactions was identified, of which cross-hypersensitivity manifested as urticaria / angioedema / anaphylaxis was observed in 127 patients. This group was divided into 2 phenotypes: a group with concomitant chronic urticaria (n=67) and without it (n=60). We assessed demographic data, drug triggers, clinical manifestations, concomitant atopy, and compared these indicators between both groups. Selected patients underwent a drug provocation test with selective or predominantly selective non-steroidal anti-inflammatory drugs and paracetamol. RESULTS: Cross-hypersensitivity reactions manifested as urticaria / angioedema / anaphylaxis is the most common phenotype of immediate-type drug cross-hypersensitivity reactions to non-steroidal anti-inflammatory drugs (75.6%). Women develop this condition 2.5 times more frequently than men, and are more likely to develop cross-drug hypersensitivity with concomitant chronic urticaria with the onset of approximately 16 years later than men. Mild manifestations of cross-hypersensitivity (urticaria/angioedema) develop more frequently than severe ones (anaphylaxis). Angioedema in children, urticaria in adults with concomitant chronic urticaria and angioedema in adults without concomitant chronic urticaria are it's main manifestations. The most frequent non-steroidal anti-inflammatory drugs triggers are metamizole, acetylsalicylic acid and propionic acid derivatives. Non-steroidal anti-inflammatory drugs with the lowest risk of developing drug hypersensitivity are coxibs, paracetamol, and to a lesser extent ― meloxicam, nimesulide. CONCLUSION: The data obtained allowed us to expand our understanding of cross-hypersensitivity reactions to non-steroidal anti-inflammatory drugs presenting as urticaria/angioedema or anaphylaxis. Selective cyclooxygenase type 2 inhibitors and paracetamol are drugs with the highest safety profile.

Applying Machine Learning and Statistical Forecasting Methods for Enhancing Pharmaceutical Sales Predictions

In today’s evolving global world, the pharmaceutical sector faces an emerging challenge, which is the rapid surge of the global population and the consequent growth in drug production demands. Recognizing this, our study explores the urgent need to strengthen pharmaceutical production capacities, ensuring drugs are allocated and stored strategically to meet diverse regional and demographic needs. Summarizing our key findings, our research focuses on the promising area of drug demand forecasting using artificial intelligence (AI) and machine learning (ML) techniques to enhance predictions in the pharmaceutical field. Supplied with a rich dataset from Kaggle spanning 600,000 sales records from a singular pharmacy, our study embarks on a thorough exploration of univariate time series analysis. Here, we pair conventional analytical tools such as ARIMA with advanced methodologies like LSTM neural networks, all with a singular vision: refining the precision of our sales. Venturing deeper, our data underwent categorisation and were segmented into eight clusters premised on the ATC Anatomical Therapeutic Chemical (ATC) Classification System framework. This segmentation unravels the evident influence of seasonality on drug sales. The analysis not only highlights the effectiveness of machine learning models but also illuminates the remarkable success of XGBoost. This algorithm outperformed traditional models, achieving the lowest MAPE values: 17.89% for M01AB (anti-inflammatory and antirheumatic products, non-steroids, acetic acid derivatives, and related substances), 16.92% for M01AE (anti-inflammatory and antirheumatic products, non-steroids, and propionic acid derivatives), 17.98% for N02BA (analgesics, antipyretics, and anilides), and 16.05% for N02BE (analgesics, antipyretics, pyrazolones, and anilides). XGBoost further demonstrated exceptional precision with the lowest MSE scores: 28.8 for M01AB, 1518.56 for N02BE, and 350.84 for N05C (hypnotics and sedatives). Additionally, the Seasonal Naïve model recorded an MSE of 49.19 for M01AE, while the Single Exponential Smoothing model showed an MSE of 7.19 for N05B. These findings underscore the strengths derived from employing a diverse range of approaches within the forecasting series. In summary, our research accentuates the significance of leveraging machine learning techniques to derive valuable insights for pharmaceutical companies. By applying the power of these methods, companies can optimize their production, storage, distribution, and marketing practices.

СИНТЕЗ И СВОЙСТВА АДАМАНТИЛСОДЕРЖАЩИХ 1,3-ДИЗАМЕЩЕННЫХ МОЧЕВИН НА ОСНОВЕ ПРОИЗВОДНЫХ ПРОПИОНОВОЙ КИСЛОТЫ - ПОТЕНЦИАЛЬНЫХ МУЛЬТИТАРГЕТНЫХ ИНГИБИТОРОВ SEH И COX-2

Known NSAIDs from the group of propionic acid derivatives (naproxen, ketoprofen and flurbiprofen) were converted by reaction with diphenylphosphoryl azide into the corresponding isocyanates with yields of 85-89%. By reacting the resulting isocyanates with (adamantan-1-yl)methylamine, adamantyl-containing ureas were synthesized in yields of 81-90 %. The resulting ureas are potential multi-target inhibitors of soluble epoxide hydrolase (sEH) and cyclooxygenase (COX).

Ibuprofen modulates tetrodotoxin-resistant persistent Na+ currents at acidic pH in rat trigeminal ganglion neurons

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to relieve various symptoms such as headache, arthralgia, and dental pain. While the primary mechanism of NSAID-based pain relief is the inhibition of cyclooxygenase-2, several NSAIDs also modulate other molecular targets related to nociceptive transmission such as voltage-gated Na+ channels. In the present study, we examined the effects of NSAIDs on persistent Na+ current (INaP) mediated by tetrodotoxin-resistant (TTX-R) Na+ channels in small-to medium-sized trigeminal ganglion neurons using a whole-cell patch-clamp technique. At clinically relevant concentrations, all propionic acid derivatives tested (ibuprofen, naproxen, fenoprofen, and flurbiprofen) preferentially inhibited the TTX-R INaP. The inhibition was more potent at acidic extracellular pH (pH 6.5) than at normal pH (pH 7.4). Other NSAIDs, such as ketorolac, piroxicam, and aspirin, had a negligible effect on the TTX-R INaP. Ibuprofen both accelerated the onset of inactivation and retarded the recovery from inactivation of TTX-R Na+ channels at acidic extracellular pH. However, all NSAIDs tested in this study had minor effects on voltage-gated K+ currents, as well as hyperpolarization-activated and cyclic nucleotide-gated cation currents, at both acidic and normal extracellular pH. Under current-clamp conditions, ibuprofen decreased the number of action potentials elicited by depolarizing current stimuli at acidic (pH 6.5) extracellular pH. Considering that extracellular pH falls as low as 5.5 in inflamed tissues, TTX-R INaP inhibition could be a mechanism by which ibuprofen and propionic acid derivative NSAIDs modulate inflammatory pain.

ω-(3-Trifluoromethylpyrazol-4-yl)alkanoic acids via (3 + 2)-cycloaddition of nitrile imines with cyclic enones and deacylative aromatization

A series of ω-substituted alkanoic acids functionalized with 1-aryl-3-trifluoromethylpyrazol-4-yl group was synthesized via two-step protocol using in situ generated CF3-nitrile imines and cyclic enones as key building blocks. The first 1,3-dipolar cycloaddition step proceeded in a fully selective manner either in solutions or under solvent-free mechanochemical activation. Treatment of the first formed cycloadducts derived from 2-cyclopentenone or 2-cyclohexenone with DDQ afforded corresponding bicyclic pyrazoles formed via dehydrogenative oxidation pathway, whereas MnO2-mediated deacylative aromatization led to desired propionic or butyric acid derivatives, respectively. In contrast, oxidation of model 2-cycloheptenone-derived (3 + 2)-cycloadduct yielded bicyclic analogue irrespectively to the applied conditions.

Molecular Docking Analysis of Novel Thiourea Derivatives of Naproxen with Potential Antitumor Activity

Abstract Naproxen, as a propionic acid derivative, causes serious gastrointestinal side effects due to the presence of free carboxylic group. In that sense, masking of carboxylic group with other pharmacophores may be a promising strategy to decrease gastrointestinal toxicity. Thiourea derivatives have been intensively investigated as potential antitumor drugs, whereby their activity is based on potential inhibition of protein kinases, topoisomerases, carbonic anhydrase and sirtuins. In addition, it was shown that inhibition of certain protein kinases might reverse resistance to chemotherapeutic drugs by enhancing the cell death in the presence of low concentrations of drug. Twenty new thiourea derivatives of naproxen were designed and their binding to four selected protein kinases involved in tumor multidrug resistance (AKT2, mTOR, EGFR and VEGFR1) was estimated using two molecular docking programs (AutoDock Vina and OEDocking). According to OEDocking, the highest potential to inhibit AKT2 and mTor has derivative 1, while derivative 20 demonstrates the highest potential towards EGFR and VEGFR1. According to AutoDock Vina, the highest potential for inhibition of EGFR, AKT2 and VEGFR1 have derivatives 16 and 17. Therefore, derivatives 1, 16, 17 and 20 are potentially the most potent protein kinase inhibitors that could be further synthesized and tested for anticancer activity.

Evaluation of the analgesic activity of new derivatives of aryl propionic acid on gastric male mice

This study focused on the recent synthesis of new compounds from aryl propionic acid derivatives compared to naproxen. The present study aimed to investigate the safety and efficiency of the new derivatives in improving analgesic effects and reducing adverse effects via modifying its chemical structure by adding new functional groups. The new compounds were characterized, and evaluate their pharmacodynamic effects. The analysis and characterization of new compounds were by 1HMNR and FT-IR spectrum. The investigation of the adverse effect after 5 days of remedy with 20 mg/kg daily administered with naproxen derivatives to the healthy male albino mice (25-30 g) for analgesic activity using the hot plate method. Mice were parted into 5 groups, consisting of the control group and 4 groups that administered naproxen or derivatives of aryl propionic acid (E, H, D1 and D2). The main tests are done by a hot plate, biochemical, macroscopic, and microscopic inspection. The results confirmed that the new drugs have potent analgesic activity. The results showed that mice administered with D1 expressed less ulcerative effect than parent naproxen, H, E and ethanol. Moreover, the number of lesions was significantly less in the D2 group, while D1-treated mice recorded no evidence of ulcers or hemorrhage in their stomachs after being examined under a dissecting microscope. The study concluded that the new D1 derivative is a compound worthy of research and future clinical applications due to its relatively high efficacy and low adverse effects compared to other derivatives prepared and tested in this study. Keywords: Analgesic, Aryl propionic acid, Naproxen, Acidity

Identification of a herbicide-resistant biotype of Echinochloa crus-galli in Ukraine

Ukraine is one of the world’s guarantors of food security and has the potential to further increase agricultural production. However, the vast majority of herbicides used on crops are acetolactate synthase (ALS) inhibitors, which poses a threat of herbicide-resistant weed species. The emergence and spread of herbicide-resistant weed biotypes can significantly increase the cost of growing crops to the point of loss of profitability. Herbicide resistance in barnyardgrass (Echinochloa crus-galli var. crus-galli) has been studied in long-term field and greenhouse experiments. Resistance of E. crus-galli to the ALS herbicide triazolopyrimidine derivative ‒ penoxsulam was identified. Expressed resistance was observed in weed plants grown from seeds collected under production conditions in Kherson region in 2015–2016 and 2020–2021. Cross resistance was observed for imidazolinone and sulfonylurea derivatives. It should be noted that the level of cross resistance to ALS herbicides was slightly higher for plants derived from weed seeds harvested in 2020–2021 compared to those harvested in 2015–2016. The introduction of a herbicidal composition of a herbicide mixture ‒ an inhibitor of 4-hydroxyphenylpyruvate dioxygenase (HPPD) (an enzyme in plants in the chain of carotenoid synthesis) ‒ mesotrione with an ALS-inhibitor (nicosulfuron) allowed effective control of the weed, which indicates the absence of multiple resistance to herbicides ‒ inhibitors of carotenoid synthesis. The high efficiency of E. crus-galli control was established by the application of herbicides ‒ inhibitors of fatty acid synthesis (graminicides). The highest level of efficiency in the experiments was observed with the application of fluazifop-butyl and somewhat less ‒ with pinoxaden. A tendency to reduce phytotoxicity to barnyardgrass from the south of Ukraine was observed with the introduction of tepraloxydim and quizalofop-ethyl. A lower level of phytotoxicity of fenoxaprop-p-ethyl on E. crus-galli should be noted compared to the effect of pinoxaden. No multiple resistance was observed with glyphosate (5-enolpyruvylshikimate-3-phosphate synthase inhibitor) and reglone (photosystem I inhibitor), allowing control of vegetative weeds at the beginning and end of the growing season. It has been established that monocot weed species have significantly increased their presence and harmfulness in agrophytocenoses in Ukraine and in the world since the 1950s with the widespread introduction of selective dicotyledonous species control with aryloxyphenoxyacetic, propionic and benzoic acid derivatives. This trend has been maintained until recently ‒ barnyardgrass is one of the dominant weed species in modern agrophytocenoses of Ukraine. Therefore, the identification of the ALS-resistant biotype of barnyardgrass complicates weed control in the following crops in rotations in the southern regions of the country: in maize crops with cross resistance to nicosulfuron, in sunflower ‒ to imidazolinones (imazamox, imazapyr), and also makes it impossible to use penoxsulam in rice production. Traditionally, the use of synthetic auxins, phenoxyacetic acid derivatives, etc. is used to control ALS-resistance. However, in Kherson region of Ukraine, already in the third year of application of rinskor (florpyrauxifen-benzyl), some weed plants were found on rice fields affected by ALS-resistant barnyardgrass, which recovered after the use of synthetic auxin. Therefore, the control of ALS-resistance (penoxsulam, etc.) in E. crus-galli with the application florpyrauxifen-benzyl in the Kherson region of Ukraine is already limited. An obvious and economically feasible preventive measure against the emergence of resistant weed biotypes is the implementation of GAP (Good Agricultural Practice, FAO) approaches: in particular, the use of high quality seeds without weed impurities, increasing the proportion of agrotechnical weed control measures, restoring and expanding crop rotations with mandatory rotation of herbicides with different modes of action, introducing dicotyledonous/leguminous crops into rotations, and using herbicides with different modes of action in crops separately or in mixtures. At the same time, agrotechnical measures and the preservation of biodiversity in agrophytocenoses should be the main factor in controlling resistance in weeds. The use of herbicides and their mixtures with different modes of action is of secondary importance. The identification of highly damaging ALS-resistant E. crus-galli in southern Ukraine indicates the insufficient effectiveness of weed control exclusively with herbicides with a single mechanism of action and requires a significant revision of the principles of crop rotation and ways of weed control in the country to maintain high levels of profitability and productivity of agrophytocenoses. Solving this problem is urgent for the preservation of Ukraine's potential as one of the guarantors of global food security.

Formulasi Self Nano-Emulsifying Drug Delivery System (SNEDDS) Ibuprofen dengan VCO dan Kombinasi Surfaktan

Ibuprofen is one of the Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) class of propionic acid derivatives which has potent anti-inflammatory and antipyretic activity. The solubility of ibuprofen is disadvantageous because it is practically insoluble and has poor dissolution. The aim of this study was to overcome the solubility of ibuprofen through a stable SNEDDS formula. One way to overcome the solubility of ibuprofen is to prepare nanoemulsions using the Self-Emulsifying Drug Delivery System (SNEDDS) technique. SNEDDS is a form of preemulsion drug which spontaneously forms nanoemulsion when it encounters the aqueous phase in the digestive tract. Parameters for the success of the SNEDDS formula include emulsification time, stability, and droplet size using a particle size analyzer (PSA). The SNEDDS formulation was carried out by mixing span 80 and tween 20, PEG 400 and VCO as the oil phase. The characteristics of SNEDDS ibuprofen include homogeneity of SNEDDS, clarity, transmittance, emulsification time, and droplet size. The composition of the optimum formula for SNEDDS ibuprofen is 1 mL of VCO; 1 mL PEG; 7 mL tween 20; 1 mL span 80. The formula shows good homogeneity, is clear with emulsification time of 15 seconds, transmittance is 92.69%, and droplet size is 221.9 nm.

The effectiveness of essential oils in the treatment of acute viral rhinosinusitis

Introduction. Acute respiratory viral infections are the most widespread diseases, accounting for up to 90% of all infectious pathology, which supports the relevance of optimizing the treatment of acute viral rhinosinusitis.Aim. Evaluate the dynamics of clinical symptoms of acute viral rhinosinusitis, which arose as part of an acute respiratory infection, when supplementing therapy with the drug Respero Myrtol (Pol-Boskamp GmbH and Co.KG, Germany), the active ingredient of which is myrtol standardized 120 mg in 1 capsule.Materials and methods. The dynamics of clinical symptoms of 20 cases of acute viral rhinosinusitis in comparison groups was analyzed. Traditional treatment of patients included taking propionic acid derivatives, ascorbic acid, intranasal use of decongestants and irrigation of the nasal cavity with isotonic saline solutions. Patients who have received traditional treatment are defined as a “standard therapy group”. To assess the effectiveness of therapy using standardized myrtol, 20 cases of acute viral rhinosinusitis against the background of acute respiratory viral infections with a similar severity were analyzed, in which patients received outpatient therapy with Respero Myrtol 2 capsules 3 times a day for 7 days in addition to the above treatment (the “myrtol therapy” group). The dynamics of the disease assessed: the number of days of disability before recovery, the period of normalization of body temperature in feverish patients, the need for vasoconstrictive intranasal agents after the seventh day of therapy, the period of complete relief of pain syndrome, the period of normalization of night sleep, the number of cases of bacterial superinfection and the need for systemic antibacterial therapy.The results. In the observed patients, the quality of sleep was restored faster, the pain syndrome was stopped earlier, less often there was a need for systemic antibiotics and prolonged use of intranasal decongestants. The disease proceeded with fewer days of disability.Conclusion. The study results have been shown to report the clinical efficacy of Respero Myrtol essential oils in the outpatient treatment of patients with acute rhinosinusitis.

Simultaneous stereoisomeric separation of loxoprofen sodium and its alcohol metabolites. Application to a stereoselective pharmacokinetic study

Loxoprofen sodium (LOX) is a propionic acid derivative non-steroidal anti-inflammatory drug (NSAID), existing in the form of four stereoisomers. The main metabolites of LOX in vivo were trans- and cis-alcohol, each consisting of four stereoisomers. The objectives of the present study were to examine the selective pharmacokinetic behavior of LOX stereoisomers and stereoselective formation of its alcohol metabolites in rats based on a chiral liquid chromatographytandem mass spectrometry (LC-MS/MS) method by using an FLM Chiral NQ-RH column, which was reported for the first time. The significant difference in pharmacokinetic parameters of four stereoisomers indicated that stereoselective behavior has occurred in rats after oral administration of LOX. (1′S,2S)-LOX showed the highest concentration among the four stereoisomers in both plasma and urine samples. Trans- and cis-alcohol metabolites of LOX were also detected in plasma and urine, and trans-alcohol was found to be primary and the stereoisomeric fractions (SFs) of its four stereoisomers at different times were calculated. Examination of the stereoisomeric composition indicated a stereo preference for (2S)-configuration with respect to trans-alcohol formation. The overall results of the present study revealed the enantioselective pharmacokinetic properties of LOX stereoisomers in rats, which provided a means to advance understanding of the complex pharmacokinetic of LOX.

Exploiting Underutilised crops

Exploiting Underutilised crops

Variations of Tween Surfactant and Propylene Glycol Cosurfactant in Topical Microemulsion Formulation on The Penetration of Ibuprofen

Ibuprofen is a derivative of propionic acid, a class of non-steroidal anti-inflammatory drugs (NSAIDs). Ibuprofen has side effects on the gastrointestinal tract. So that topical use can be a solution to reduce the side effects of oral use because of the release of topical drugs through the stratum corneum which makes it selective in certain places. The preparation chosen was a topical microemulsion because it is more thermodynamically stable and has no effect on the gastrointestinal tract. This study aims to determine the effect of the ratio of surfactant concentrations of various ratios of tween 20:tween 80 and cosurfactant propylene glycol to the penetration rate of ibuprofen across the membrane and to determine the physical characteristics of topical microemulsions. Selection of tween surfactant and propylene glycol cosurfactant because it has high physical stability. This research is an experimental study, namely by making four formulations with various ratios of surfactant and cosurfactant with a difference of 2.5% in each formulation of topical ibuprofen microemulsion with a concentration of 5% ibuprofen using variations of surfactant tween 20 and tween 80, cosurfactant propylene glycol with black cumin oil phase. Evaluation of the preparation by organoleptic test, pH test of the preparation, examination of the type of emulsion, particle size measurement, microemulsion release test in vitro using the Franz diffusion method. The results show that the concentration ratio of surfactant tween 20:tween 80 and cosurfactant propylene glycol can affect particle size, pH and penetration velocity (flux) in Franz diffusion. The results of the study showed that in F1 using surfactant tween 20:tween 80 with a concentration of 71.6% (6:4) had the smallest particle size of 11.5 nm and the largest flux value was 128.45 g.cm-2.H- 1. In conclusion, variations in surfactant and cosurfactant concentrations can affect the pH of the preparation, particle size, penetration speed (flux). The results obtained that the cumulative percent and penetration speed of all formulas had significant differences (p&lt;0.05).

Synthesis, Characterization of New Isatin-Ibuprofen Derivatives with Expected Biological Activity

Ibuprofen is one of the most important members of NSAIDs, named aryl propionic acid derivative. Isatin (1H-indole-2,3-dione) is an important molecule of heterocyclic compounds that have many biological activities. This work illustrates the synthesis of new ibuprofen-isatin derivatives by connecting ibuprofen hydrazide with different isatin derivatives by a condensation reaction, followed by characterization by fourier-transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance (1H-NMR) spectroscopy. The anti-inflammatory activity was evaluated by using the egg-white induce edema method for all the synthesized compounds (5-8), the compounds 5 and 6 showed better anti-inflammatory activity than ibuprofen as a standard compound. Their antimicrobial activity was evaluated and compared with ciprofloxacin, ampicillin, and fluconazole; the compounds 5 and 7 have moderate antibacterial activity against gram-positive and gram-negative bacteria, with lower antifungal activity.

Phytoconstituent estimation and LC-MS studies of field grown Withania somnifera (L.) Dunal root extract in Jharkhand and Bihar

Plants in either raw form or their root extracts are utilized as complementary and alternative medicine in various disorders. The present study was undertaken for phytoconstituents estimation and to evaluate chemical compositions of methanolic extract of Withania somnifera (L.) Dunal (Ashwagandha) roots collected from BAU, Ranchi, Jharkhand and Sabour, Bhagalpur, Bihar. Phytochemicals through crude methanolic extract were analyzed in Ashwagandha roots. Alcoholic extract was prepared using Soxhlet extraction apparatus. On phytochemical evaluation, total phenolic, flavonoid, total tannin and alkaloids were estimated. Presence of bioactive components in extract was determined by Liquid Chromatography-Mass Spectrophotometry (ESI positive ion) technique. Qualitative screening of extract ensured the presence of alkaloids, phenols, tannins and flavonoids. Quantitatively these phytochemicals showed TPC (66.06 mg/gm), TFC (650.0 mg/gm), TAC (102 mg/gm) and TTC (5.89 mg/gm). However, the phytochemicals and yield did not accumulate in various fractions on polarity. This result was supported by LC-MS analysis which showed 17 definite peaks in their chromatogram but only 8 peaks offer a suitable approximation. Extract revealed forty five bioactive compounds where most of them were phenolic compounds, aryl propionic acid and cinnamide derivatives. Quantitative analysis of present phytochemical showed maximum quantity of TFC followed by TAC, TPC and TTC. On the other hand, presence of various bioactive compounds in root extract showed that plant is having very high medicinal value.

Screening of potent α-glucosidase inhibitory and antioxidant polyphenols in Prunella vulgaris L. by bioreaction-HPLC-quadrupole-time-of-flight-MS/MS and in silico analysis.

Prunella vulgaris L. is a well-known traditional Chinese medicine for blood glucose homeostasis and antioxidant potential. Ethyl acetate fraction of P. vulgaris L. demonstrated higher phenolic content (85.53 ± 6.74mg gallic acid equivalents per gram dry weight), α-glucosidase inhibitory (IC50 , 69.13 ± 2.86 μg/ml), and antioxidant (IC50 , 8.68 ± 1.01 μg/ml) activities. However, the bioactive polyphenols responsible for the beneficial properties remain unclear. Here, bioreaction-HPLC-quadrupole-time-of-flight-MS/MS method was developed for rapid, accurate, and efficient screening and identification of polyphenols with α-glucosidase inhibitory and antioxidant activities from P. vulgaris L. Bioactive polyphenols can specifically bind with α-glucosidase or react with 1,1-diphenyl-2-picryl-hydrazyl radical, which was easily discriminated from nonactive compounds. Subsequently, 20 bioactive polyphenols (16 phenyl propionic acid derivatives and four flavonoids) were screened and identified. Furthermore, molecular docking analysis revealed that screened 20 polyphenols bind with the active sites of α-glucosidase through hydrogen bonding and π-π stacking. Density functional theory calculations demonstrated their electron transport ability and chemical reactivity. The in silico analysis confirmed the screened results. In summary, this study provided a valuable strategy for rapid discovering bioactive compounds from complex natural products and offered scientific evidence for further development and application of P. vulgaris L.