Drug Diclofenac Research Articles

Microwave‐Assisted Tragacanth Gum–Based Grafted Silver Nanocomposite Hydrogel for Sustained Release Formulations of Diclofenac Sodium and Antibacterial Assay

ABSTRACTIn this work, novel tragacanth gum‐graft‐poly(2‐acrylamido‐2‐methylpropanesulfonic acid) (TG‐g‐PAMPS) hydrogel was synthesized via free radical copolymerization of TG, 2‐acrylamido‐2‐methylpropanesulfonic acid by using ammonium peroxodisulfate and N,N‐methylene‐bis‐acrylamide under microwave radiation, resulting in the cross‐linked graft copolymer network. Silver nanoparticles (SNs) were formed and stabilized by the reduction of silver nitrate using tri‐sodium citrate. The TG‐g‐PAMPS gel and its nanocomposite were characterized and confirmed using FTIR, TGA, XRD, SEM, EDS, and TEM techniques. It is observed that the presence of SNs significantly improves the swelling ability of the TG‐g‐PAMPS gel. Degradation studies of both hydrogels were studied using the soil burial method and determining the respective weight loss. The presence of SNs is found to impart significant antibacterial properties to the gel against Pseudomonas aeruginosa and Escherichia coli bacteria. Further, the TG‐g‐PAMPS gel and TG‐g‐PAMPS‐SN were evaluated as matrix materials for the release of the drug (diclofenac sodium) and the effect of SNs on the release was examined. The in‐vitro released data were analyzed using empirical equations to understand the mechanism of release. Among the various models, the released data were well fitted into the Korsmeyer–Peppas equation and the released kinetics followed non‐Fickian diffusion.

Solid-State Microfabricated Potentiometric Sensors for Selective Assessment of Diclofenac Sodium Utilizing Pentafluorophenyl Diazonium Modified Carbon Nanotubes Transducer Layer

In the pharmaceutical field, analytical chemistry is evolving and one area that is experiencing enthusiasm is the design and implementation of solid contact ion-selective electrodes. We have developed two potentiometric sensors for the selective assay of a widely used drug diclofenac sodium. Diclofenac sodium was targeted in one of its most recommended dosage forms (Arthrotec® tablets) in the presence of misoprostol. A cost-effective copper printed circuit board as a substrate has been coated with a PVC sensing membrane to fabricate sensor I. Hydrophobic carbon nanotubes (CNTs) have been modified through in situ reduction of pentafluorophenyl diazonium using sodium borohydride. An interlayer of the modified CNTs was inserted as a transducer layer between the Cu substrate and the ion-sensing membrane in sensor II to enhance its electrochemical performance and stability. The microfabricated electrodes demonstrated encouraging outcomes upon the direct assay of diclofenac sodium in combination with misoprostol and other additives without sample preparation steps. The responses presented a linear Nernstian pattern in the range of 1.0 × 10−4 to 1.0 × 10−2 mol l−1 with a slope of −58.2 and −58.4 mV/decade for sensors I and II, consequently. Finally, the sustainability of the developed technique was assured using advanced green metrics.

New Method for Obtaining Carboxylic Derivatives of Oxazolo[5,4-b]pyridine Based on 3-Aminopyridine-2(1H)-ones

Current methods for synthesis of oxazolo[5,4-b]- and oxazolo[4,5-b]pyridines have several limitations, such as severe reaction conditions, lengthy reaction times, low yields and concurrent formation of side reaction products. This article presents the results of study focused on a one-step method for the synthesis of new derivatives of oxazolo[5,4-b]pyridine incorporating an aliphatic carboxylic group as a linker. During the investigation of acylation reactions of 3-aminopyridine-2(1H)-ones with cyclic anhydrides of dicarboxylic acids (succinic, maleic and glutaric), it was found that the monoamides formed at the initial stage undergo intramolecular cyclization yielding derivatives of oxazolo[5,4-b]pyridine. Subsequently, the reaction conditions were studied and optimized to achieve the target compounds with high yield and purity. The potential anti-inflammatory activity of the obtained derivatives of oxazolo[5,4-b]pyridine was evaluated by molecular docking method using AutoDock Vina software. Compounds 11-14b exhibited higher binding affinity with the selected target protein Prostaglandin synthase-2 (1CX2) compared to the reference anti-inflammatory drug diclofenac. Thus, taking into account the results of in silico analyses, the newly synthesized oxazolo[5,4-b]pyridine derivatives based on 3-aminopyridine-2(1H)-ones are promising candidates for further investigation of their potential anti-inflammatory activity through in vivo methods.

Mytilus galloprovincialis: A valuable bioindicator species for understanding the effects of diclofenac under warming conditions

Drugs are chemical compounds used to treat and improve organic dysfunctions caused by diseases. These include analgesics, antibiotics, antidepressants, and antineoplastics. They can enter aquatic environments through wastewater streams, where their physico-chemical properties allow metabolites to distribute and accumulate. Current climate change and associated extreme weather events may significantly impact these substances' toxicity and aquatic organisms' sensitivity. Among the chemicals present in aquatic environments is the non-steroidal anti-inflammatory drug diclofenac (DIC), which the EU monitors due to its concentration levels. This study investigated the influence of temperature (control at 17 °C vs. 21 °C) on the effects of DIC (0 μg/L vs. 1 μg/L) in the mussel species Mytilus galloprovincialis. Significant results were observed between 17 and 21 °C. Organisms exposed to the higher temperature showed a decrease in several parameters, including metabolic capacity and detoxification, particularly with prolonged exposure. However, in some parameters, after 21 days, the M. galloprovincialis showed no differences from the control, indicating adaptation to the stress. The results of this study confirm that DIC concentrations in the environment, particularly when combined with increased temperatures, can produce oxidative stress and adversely affect M. galloprovincialis biochemical and physiological performance. This study also validates this species as a bioindicator for assessing environmental contamination with DIC. Beyond its direct impact on aquatic organisms, the presence of pharmaceuticals like DIC in the environment highlights the interconnectedness of human, animal, and ecosystem health, underscoring the One Health approach to understanding and mitigating environmental pollution.

Reversible switchable deep eutectic solvent for dispersive liquid–liquid microextraction of non-steroidal anti-inflammatory drugs in biological and wastewater samples combined with high-performance liquid chromatography

The development of fast and simple bioanalytical methods for determining drugs is increasing. In the present study, a pH-induced reversible switchable deep eutectic solvent based on dispersive liquid–liquid microextraction was assessed (sDES-DLLME) for the analysis of three non-steroidal anti-inflammatory drugs (salicylic acid, mefenamic acid, and diclofenac) in plasma, urine and wastewater samples and their analysis by high-performance liquid chromatography. In this study, the switching process of DES (sDES) composed of 2-isopropyl-5-methylphenol (thymol) and a fatty acid was performed by pH adjustment. By adding NaOH to the sample solution, a homogeneous phase was achieved based on the hydrophilic form of sDES, and a two-phase system was obtained by adding an inorganic acid (HCl) to return the hydrophobicity. The important factors, such as DES type, the DES volume and the conditions of NaOH and HCl solutions were perused. Under optimal conditions, the limits of detection and limits of quantification were acquired in the range from 1 to 3 μg L−1 and 3 to 9.2 μg L−1 for three analytes, respectively. The ER% and EF values were to be in the range of 93.3 to 97.2 % and 112 to 117 for all analytes. A good linear range was declared up to 500 μg L−1 while the precision (%RSD) as the inter-day and intra-day in different samples was in the range of 4.6–6.1 % and 2.7–5.1 % respectively. Subsequently, the developed method was utilized to analyze the drugs in human urine, plasma and wastewater samples.

Re-assessment of monoclonal antibodies against diclofenac for their application in the analysis of environmental waters.

The non-steroidal anti-inflammatory drug (NSAID) diclofenac (DCF) is an important environmental contaminant occurring in surface waters all over the world, because, after excretion, it is not adequately removed from wastewater in sewage treatment plants. To be able to monitor this pollutant, highly efficient analytical methods are needed, including immunoassays. In a medical research project, monoclonal antibodies against diclofenac and its metabolites had been produced. Based on this monoclonal anti-DCF antibody, a new indirect competitive enzyme-linked immunosorbent assay (ELISA) was developed and applied for environmental samples. The introduction of a spacer between diclofenac and the carrier protein in the coating conjugate led to higher sensitivity. With a test midpoint of 3 μg L-1 and a measurement range of 1-30 μg L-1, the system is not sensitive enough for direct analysis of surface water. However, this assay is quite robust against matrix influences and can be used for wastewater. Without adjustment of the calibration, organic solvents up to 5%, natural organic matter (NOM) up to 10 mg L-1, humic acids up to 2.5 mg L-1, and salt concentrations up to 6 g L-1 NaCl and 75 mg L-1 CaCl2 are tolerated. The antibody is also stable in a pH range from 3 to 12. Cross-reactivity (CR) of 1% or less was determined for the metabolites 4'-hydroxydiclofenac (4'-OH-DCF), 5-hydroxydiclofenac (5-OH-DCF), DCF lactam, and other NSAIDs. Relevant cross-reactivity occurred only with an amide derivative of DCF, 6-aminohexanoic acid (DCF-Ahx), aceclofenac (ACF) and DCF methyl ester (DCF-Me) with 150%, 61% and 44%, respectively. These substances, however, have not been found in samples. Only DCF-acyl glucuronide with a cross-reactivity of 57% is of some relevance. For the first time, photodegradation products were tested for cross-reactivity. With the ELISA based on this antibody, water samples were analysed. In sewage treatment plant effluents, concentrations in the range of 1.9-5.2 μg L-1 were determined directly, with recoveries compared to HPLC-MS/MS averaging 136%. Concentrations in lakes ranged from 3 to 4.4 ng L-1 and were, after pre-concentration, determined with an average recovery of 100%.

Assessment of <i>In vitro</i> antioxidant and Analgesic activity of Ethyl acetate fraction of <i>Urena Lobata</i> leaves

Background: The primary aim of this study is to identify the most active fraction from Urena lobata leaves and subsequently evaluate the analgesic and antioxidant accomplishments of the identified potent extract. The focus is on determining the fraction with the highest efficacy for potential therapeutic applications. Methods: U. lobata leaves were consecutively extracted with solvents like n-hexane, chloroform, ethyl acetate, and methanol. The concentrated fractions underwent initial phytochemical screening. The fraction exhibiting the highest activity, as determined by the carrageenan model, was further evaluated for its analgesic potential through the hot plate and acetic acid-induced writhing methods. In-vitro antioxidant activity was evaluated through DPPH and FRAP assays. Results: The preliminary phytochemical analysis of U. lobata leaf fractions exposed the presence of steroids, triterpenes, alkaloids, carbohydrates, tannins, and flavonoids. In the carrageenan-induced hind paw edema model, the ethyl acetate fraction of U. lobata leaf (ULEAF) demonstrated the highest anti-inflammatory effects, comparable to the standard drug Diclofenac sodium. Evaluation of analgesic potential using the hot-plate method and acetic acid-induced writhing test showed dose-dependent efficacy, with 500 mg/kg ULEAF exhibiting effects similar to ibuprofen. In vitro, antioxidant assays indicated potent radical scavenging and reducing power in the ethyl acetate fraction. Conclusion: In conclusion, U. lobata leaf fractions exhibited potent anti-inflammatory properties, with the ethyl acetate fraction demonstrating notable analgesic and antioxidant activity. These findings support the plant’s therapeutic potential for further exploration in pharmaceutical development.

Pharmacognostical Evaluation, In-vitro Anti-Inflammatory and Anti-Arthritic Activities of Sageraea laurina Dalzell

Aim: Present investigation performed pharmacognostical evaluation, extraction, and evaluation of anti-inflammatory as well as anti-arthritic activities of Sageraea laurina Dalzell leaves. Materials and methods: Pharmacognostical evaluation was carried out for morphology and microscopy of Sageraea laurina Dalzell leaf and its powder, followed by determination of proximate values. Ethanolic (SLLE) as well as aqueous extract of leaves (SLLA) were evaluated for phytochemical screening, and in-vitro anti-inflammatory activity against MMP-2 (gelatinase-A) along with MMP-9 (gelatinase-B) by gelatin zymography as well as in-vitro anti-arthritic activity by egg albumin protein denaturation approach. Total phenolic as well as flavonoid content of extract were assessed. Percentage inhibition for protein denaturation was calculated. Results: Microscopical study of leaves showed presence of abaxial midrib, palisade parenchyma cells, phloem elements, xylem elements, spongy parenchyma, cystoliths, lithocysts, glandular trichomes, collenchyma cells thick lamina diacytic type of stomata and vessel elements. Phytochemical screening divulged existence of carbohydrates, flavonoids, steroids, alkaloids, saponin glycosides, tannins and phenolic compounds. Copious of phenolic compounds were noted in SLLE which were 89.42mg gallic acid equivalent/g (GAE/g dry weight) along 86.21mg QUE/g quercetin equivalent /g (QUE/g dry weight). Coomasie blue staining revealed proteolysis sites as translucent bands on dark blue background. Percentage inhibition for anti-inflammatory activity for SLLE against MMP-2 and MMP-9 was found to be 62% and 56% respectively, for SLLA against MMP-2 and MMP-9 was found to be 34% and 32% respectively. Egg albumin denaturation method, displayed percentage inhibition at concentration of 500µg/ml for SLLE and SLLA 74.14 and 60.30 respectively, standard drug diclofenac sodium at same concentration was found to be 84.53%. It was found that SLLE was more potent in inhibition of egg albumin denaturation than diclofenac sodium. Conclusion: Findings of present investigation revealed possession of significant in-vitro anti-inflammatory and antiarthritic activities by Sageraea laurina Dalzell leaves and serves as a natural biomedicinal remedial agent treating inflammation and rheumatism.

Assessment of antibacterial, anti-inflammatory, and anti-cancer activities of Melia azedarach L. leaf extract

The purpose of the present study was to evaluate the antibacterial, anti-inflammatory, and cytotoxic properties of Melia azedarach leaf. The phytoconstituents found in the leaves were extracted with four different solvent systems based on their polarity index. Antimicrobial activity of selected plant extracts was evaluated using disc diffusion and micro-broth dilution methods against four different pathogenic bacterial strains. The ethanolic extract of M. azedarach leaf showed a significant inhibitory effect on the growth of Escherichia coli (15.07 mm) and Staphylococcus aureus (18.23 mm) (P < 0.005), followed by Bacillus subtilis and Salmonella typhi. Further, the mechanism of action was confirmed by live/dead cells analysis, which revealed the death of E. coli and S. aureus upon treatment with ethanolic extract. In vivo anti-inflammatory test conducted using carrageenan-induced rat paw edema model revealed that the 300 mg/kg ethanolic extract exhibited a significant anti-inflammatory activity of 51.78% compared with that of standard drug diclofenac (P < 0.001). Further, the cytotoxicity of ethanolic extract against human hepatocarcinoma cell lines (HepG2) was evaluated by MTT assay, and the findings showed a moderate level of toxicity against the HepG2 cell line with an IC50 value of 540.00 ± 0.6 μg/mL compared to doxorubicin. HepG2 cells treated with doxorubicin (2 μg/mL) and ethanolic extract showed a 2.33- and 1.35-fold increase in p53 gene expression, respectively. Apoptosis activity was measured in terms of DNA laddering, which indicated the late stage of apoptosis. The results showed that the extract-treated cell lines induced DNA fragmentation, which was found to be a potent anti-cancer mechanism in HepG2 cells. This study corroborated that the leaf extract of M. azedarach is a good source of active phytochemicals, with promising biological activities.

Anti-inflammatory activity of the phenol rich fraction of Garcinia pedunculata Roxb (ex. Buch Ham): an in vitro and in vivo study.

Garcinia pedunculata, a tropical plant found abundantly in the north-east region of India, has been used by many traditional healers for various gastrointestinal ailments. Studies are being carried out for the proper pharmacological identification of the compounds as well as the mode of action for the treatment of various diseases. In this study, phytochemistry of the fruit was evaluated, followed by a quantitative analysis of the total phenolic and flavonoid content of the methanolic crude extract as well as different fractions (n-hexane, chloroform, ethyl acetate, and n-butanol). The fraction with the most potent flavonoid and phenolic content was evaluated for its anti-inflammatory activity using both in vitro and in vivo assays. The chloroform fraction of G. pedunculata fruit extract was found to have a substantial amount of phenols and flavonoids. This fraction inhibited the denaturation of BSA and significantly stabilized human RBC membrane compared to the standard drug Diclofenac sodium. The fraction also significantly reduced the formaldehyde-induced paw edema in mice and normalized the blood parameters. This study provides evidence that G. pedunculata fruit extract plays a critical role in anti-inflammatory activity, indicating that it can be a potential candidate for further investigation in the treatment of inflammation-related diseases.

A Splendid comprehension into in-silico and in-vitro biological investigations to assess the anti-inflammatory and anti-breast cancer activities of newly synthesized 1-Phenylethyl Quinoline-4-carboxylates

Well-designed and differently substituted biodegradable architecture of 1-phenylethyl 2-phenylquinoline-4-carboxylates (MP1-MP9) have been synthesized in excellent yields exploiting Steglich esterification techniques and purified by flash column chromatography. FT-IR, 1H NMR, 13C NMR spectral techniques and mass spectrometry were used to characterise the synthesized compounds MP1-MP9. In addition, in-silico ADMET characteristics and molecular docking analysis of MP1-MP9 were also carried out by different computational investigations. Molecular docking analysis were established against three different types of proteins, viz. analgesic (1JNQ), anti-inflammatory (4YK5) and anti-breast cancer active protein (1DZA) downloaded from protein data bank and found best suited for anti-inflammatory and anti-breast cancer activity with impressive binding energy values. The in-vitro anti-inflammatory activity was performed against five selected analogues MP1, MP3, MP5, MP6 and MP8, in which compound MP3 possess a good IC50 value of 88.88 µM on comparing with standard drug diclofenac sodium. Further, an in-vitro anti-breast cancer study using MTT assay method against five selected drug like analogues MP1, MP2, MP4, MP7, and MP9 were executed and MP1 having unsubstituted phenyl ring showed higher anti-breast cancer activity with a very good IC50 value of 50.30 µM. All the results obtained for anti-breast cancer activity were compared with the standard drug 5-Flurouracil (5-FU).

Understanding treatment of pain during SARS-CoV-2 pandemic in a two-year intercity longitudinal study using wastewater-based epidemiology

SARS-CoV-2 pandemic had a significant impact on the society, economy, and health of people around the world with consequences that need to be better understood for future pandemic preparedness. This manuscript provides insights into the usage of pharmaceuticals for pain treatment management throughout SARS-CoV-2 pandemic. Four towns and cities with a total population of > 1 million people covering an area of 2000 km2 in South West England were monitored for twenty-four months. Results showed different patterns in pain pharma usage, with small towns having higher population normalised daily loads (PNDLs) than big cities for majority of pain killers studied. This is likely due to demographics of these cities with smaller cities having older population. Per capita consumption of non-steroidal anti-inflammatory drugs (NSAIDs) increased compared to pre-pandemic usage in line with SARS-CoV-2 infections (ibuprofen and acetaminophen), while body pain drugs (diclofenac and naproxen) decreased in line with restrictions and closure of sports facilities. Changes in population normalised daily intake (PNDI) of pain killers were particularly apparent during the 1st and 3rd national lockdown. Comparison of PNDIs with prescriptions highlighted differences related to medication availability (OTC drugs) and patients’ nonadherence (prescribed drugs). In addition, several instances of direct disposal events across the catchments were observed which raises an issue of lack of pharma compliance and general understanding of potential environmental impacts from pharma usage.

Design, Synthesis, Molecular Docking, and Anti‐Inflammatory Potential of Amide Coupling Carboxylate Derivatives

AbstractEight new amide‐based carboxylate derivatives were synthesized and evaluated for anti‐inflammatory potentials using in‐vitro, in‐vivo and in silico studies. In cyclooxygenase‐2 assay, maximum percent antagonist potential was exhibited by sodium 4‐((4‐fluorophenyl) amino)‐4‐oxobutanoate (93.91 %), bis ((4‐((4‐methoxy‐2‐nitrophenyl)amino)‐4‐oxobutanoyl)oxy) zinc (93.04 %), and bis ((4‐((4‐bromo‐2‐fluorophenyl) amino)‐4‐oxobutanoyl)oxy)zincio (2‐bromopyridine) (92.64 %) with IC50 values of 1.65, 2.08, and 0.288 μM/ml respectively. Celecoxib demonstrated 98.60 % effect with an IC50 value of 0.041 μM/ml. In LOX assay, 4‐((4‐methoxy‐2‐nitrophenyl)amino)‐4‐oxobutanoic acid (97.03 %), bis ((4‐((4‐methoxy‐2‐nitrophenyl)amino)‐4‐oxobutanoyl)oxy)zinc (95.45 %), and (92.53 %) demonstrated maximum percent effect with IC50 values 3.48, 0.45, and 0.83 μM/ml respectively. The standard 5‐lipoxygenase inhibitor (montelukast) resulted from a 98.39 % inhibitory effect with an IC50 value of 0.194 μM/ml. In in‐vivo analysis, the potent tested compounds (5, 10, and, 20 mg/kg) significantly (p<0.001) reversed the induced edema by carrageenan. The standard drug aspirin displayed significant results (74–83 %). The standard drugs in these phlogestic agents displayed excellent results like cetirizine (67.9 %), celecoxib (81.61 %), icatibant (82.22 %) and nemesulide (87.17 %) at 5th h. The compounds displayed the inhibitory potential against targeted proteins. 4‐((4‐methoxy‐2‐nitrophenyl)amino)‐4‐oxobutanoic acid, 4‐((4‐fluorophenyl)amino)‐4‐oxobutanoic acid and sodium 4‐((4‐bromo‐2‐fluorophenyl)amino)‐4‐oxobutanoate shown excellent behavior by giving negative binding energies close of standard drugs montelukast (5F1A: −7.9 kcal/mol) and diclofenac (3O8Y: −8.5 Kcal/mol). The tested compounds were proven significant anti‐inflammatory potentials.

Design, synthesis, biological assessment and molecular modeling studies of novel imidazothiazole-thiazolidinone hybrids as potential anticancer and anti-inflammatory agents

A new series of imidazothiazole derivatives bearing thiazolidinone moiety (4a-g and 5a-d) were designed, synthesized and evaluated for potential epidermal growth factor receptor (EGFR) kinase inhibition, anticancer and anti-inflammatory activity, cardiomyopathy toxicity and hepatotoxicity. Compound 4c inhibited EGFR kinase at a concentration of 18.35 ± 1.25 µM, whereas standard drug erlotinib showed IC50 value of 06.12 ± 0.92 µM. The molecular docking, dynamics simulation and MM-GBSA binding energy calculations revealed strong interaction of compound 4c with binding site of EGFR. The synthesized compounds were evaluated for their anticancer activity by MTT assay against three human cancer cell lines A549 (Lung), MCF-7 (Breast), HCT116 (Colon), one normal human embryonic kidney cell line HEK293 and also for their EGFR kinase inhibitory activity. Few compounds of the series (4a, 4b, 4c) showed promising growth inhibition against all the tested cancer cell lines and against EGFR kinase. Among these, compound 4c was found to be most active and displayed IC50 value of 10.74 ± 0.40, 18.73 ± 0.88 against cancer cell lines A549 and MCF7 respectively whereas it showed an IC50 value of 96.38 ± 1.79 against HEK293 cell line indicating lesser cytotoxicity for healthy cell. Compounds 4a, 4b and 4c were also examined for their apoptosis inducing potential through AO/EB dual staining assay and it was observed that their antiproliferative activity against A549 cells is mediated via induction of apoptosis. Cardiomyopathy studies showed normal cardiomyocytes with no marked sign of pyknotic nucleus of compounds 4b and 4c. Hepatotoxicity studies of compounds 4b and 4c also showed normal architecture of hepatocytes. Compounds 4a-g and 5a-d were also evaluated for their in-vitro anti-inflammatory activity by protein albumin denaturation assay. Among the tested compounds 4a-d and 5a-b showed promising activity and were selected for in-vivo inflammatory activity against carrageenan rat paw edema test. Among these compounds, 4b was found to be most active in the series showing 84.94% inhibition, whereas the standard drug diclofenac sodium showed 84.57% inhibition. Compound 4b also showed low ulcerogenic potential and lipid peroxidation. Thus, compounds 4c and 4b could be a promising lead compounds for developing anticancer and anti-inflammatory agents with low toxicity and selectivity.

SYNTHESIS AND ANALGESIC ACTIVITY OF METHYL-1-ANTIPYRYL-4-AROYL-2,3-DIOXO-2,3,5,10-TETRAHYDROBENZO[B]PYRROLO[2,3-E][1,4]DIAZEPINE-10A(1H) –CARBOXYLATES

In order to obtain new biologically active compounds, methyl-1-antipyryl-4-aroyl-2,3-dioxo-2,3,5,10-tetrahydrobenzo[b]pyrrolo[2,3-e][1,4]diazepine was synthesized-10a(1H)-carboxylates by reacting 1-antipyryl-4-aroyl-5-methoxycarbonyl-1H-pyrrole-2,3-diones with o-phenylenediamine. The structures of the obtained compounds were confirmed by 1H NMR, IR spectroscopy, X-ray diffraction and elemental analysis. The presence of several electrophilic centers in the structure of antipyryl-substituted 1H-pyrrole-2,3-diones gives them a high reactivity with respect to binucleophilic reagents. Apparently, the described interaction is carried out by the initial nucleophilic attack of one aminogroup of o-phenylenediamine on the C5 carbon atom of the pyrrole-2,3-dione ring, followed by the attack of another aminogroup on the carbonyl carbon atom of the aroyl fragment, closing the diazepine ring. The described reaction is a convenient preparative method for the synthesis of previously undescribed methyl-1-antipyryl-4-aroyl-2,3-dioxo-2,3,5,10-tetrahydrobenzo[b]pyrrolo[2,3-e][1,4]diazepine-10a(1H)-carboxylates, which are of interest as pharmacological substances. The described interaction proceeds quickly and with high yields. The obtained compounds were screened for analgesic activity, as a result of which a more pronounced effect was found in some products compared to the reference drug (diclofenac sodium). A preliminary assessment of acute toxicity was carried out, according to which the derivatives of 2,3,5,10-tetrahydrobenzo[b]pyrrolo[2,3-e][1,4]diazepine proved to be safe for further studies. The survival rate of animals in all groups is 100% after 24 h and 100% after 14 days. Screening of analgesic activity was performed by the hot plate method. Registration of time was carried out from the moment of placement on a hot surface until the appearance of a behavioral response to nociceptive stimulation 60 and 120 min after the administration of substances. For citation: Lyadov V.A., Makrushin D.E., Denislamova E.S., Maslivets A.N., Triandafilova G.A., Solodnikov S.I. Synthesis and analgesic activity of methyl-1-antipyryl-4-aroyl-2,3-dioxo-2,3,5,10-tetrahydrobenzo[b]pyrrolo[2,3-e][1,4]diazepine-10a(1H) –carboxylates. ChemChemTech [Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol.]. 2024. V. 67. N 5. P. 17-23. DOI: 10.6060/ivkkt.20246705.6939.

Isolation, characterization and pharmacological potentials of methanol extract of Cassia fistula leaves: Evidenced from mice model along with molecular docking analysis

The purpose of the current investigation was to conduct a detailed analysis of the chemical components and medicinal properties of the methanolic crude extract derived from the leaves of Cassia fistula. This analysis was carried out using both experimental (in vivo) and computational (in silico) methods. Eleven chemicals were chromatographically isolated using GC-MS/MS, which utilizes a library of NIST and Wiley 2020 versions. FTIR analysis of the extract was performed to identify the functional group of the compounds. The glucose-lowering capacity, analgesic, and anti-diarrheal activities of methanolic crude extract were analyzed utilizing a well-known oral glucose tolerance test, tail immersion method, writhing assay, and castor oil-induced diarrheal mice methods, respectively. After 60 min, 120 min, and 180 min of loading the drugs, a significant reduction of blood glucose levels was examined (p < 0.05) in all the extracts of this plant (200 mg/kg, 400 mg/kg and 600 mg/kg) utilized in this research at a time-dependent manner. Similarly, all the crude extracts showed significant (p < 0.05) effects against pain centrally and peripherally compared to the standard drug morphine (2 mg/kg bw) and diclofenac sodium (50 mg/kg bw). Moreover, the methanol extract (400 mg/kg bw) manifested anti-diarrheal efficacy by inhibiting 72.0 % of the diarrheal episode in mice compared to the standard drug loperamide (inhibition = 80.0%). The results of the computational investigations corroborated existing in-vivo findings. Greater or close to equivalent binding affinity to the active binding sites of kappa opioid receptor, glucose transporter 3 (GLUT 3), and cyclooxygenase 2 was indicative of the potential anti-diarrheal, hypoglycemic, and analgesic characteristics of the isolated compounds (COX-2). Moreover, anticancer and antimicrobial potentiality was also found impressive through evaluation of binding affinity with epidermal growth factor receptor (EGFR) and dihydrofolate reductase (DHFR) receptors. Results from this study indicated that C. fistula might be a beneficial natural resource for treating diarrhea, hyperglycemia, and pain. However, additional research is required to conduct a comprehensive phytochemical screening and establish precise action mechanisms of the crude extract or the plant-derived compounds.

Combining Carbon Materials and Ionic Liquid Gels to Boost Simultaneous Removal of Emerging Pollutants from Wastewaters

AbstractWater bodies contamination is a pressing issue of modern society, exacerbated by the large structural variety of contaminants. This explains the interest toward developing systems able to remove from wastewater different contaminants, with different susceptibility to removal methods. Consequently, herein hybrid ionic liquid gels, based on 1,3:2,4‐dibenzylidene‐D‐sorbitol (DBS), doped with graphite, carbon nanotubes, graphene, and graphene oxide, are described. First, the gel–sol transition temperatures (Tgel), rheological and self‐healing properties are determined. These gels are then used as sorbent materials and, for the first time, for removing mixtures of pollutants of different classes, namely the dyes rhodamine B and methyl orange, the drugs diclofenac and carbamazepine, or the endocrine disruptor bisphenol A, to simulate real wastewaters. Interestingly, hybrid gels prove efficient in removing single and mixed pollutants. The best performing gel is reusable for at least 12 consecutive cycles, without any intermediate washing. It can also be embedded in adsorption columns or dialysis membranes, to treat larger volumes of wastewater. Here, this gel achieves an adsorption capacity of 117 and 66 mg g−1 for rhodamine B and bisphenol A in mixture, with a distinct preference toward cationic contaminants, exhibiting competitive performance with most systems previously reported.

Green Synthesis of Metal-Doped ZnO Nanoparticles Using Bauhinia racemosa Lam. Extract and Evaluation of Their Photocatalysis and Biomedical Applications.

A fascinating problem in the fields of nanoscience and nanobiotechnology has recently emerged, and to tackle this, the production of metal oxide nanoparticles using plant extracts offers numerous benefits over traditional physicochemical methods. In the present investigation, ZnO nanoparticles were fabricated from Bauhinia racemosa Lam. (BR) leaves extract with various transition metal (TM) dopants (Ni, Mn, and Co). Plant leaves extract containing metal nitrate solutions were utilized as a precursor to synthesize the pristine and TM-doped ZnO nanoparticles. Structural, functional, optical, and surface properties of the fabricated samples were studied by using physicochemical and photoelectrochemical measurements. The organic pollutants tetracycline (TC), ampicillin (AMP), and amoxicillin (AMX) were used in the photocatalytic degradation assessment of the fabricated samples. Through X-ray diffraction (XRD) and transmission electron microscopy (TEM) investigation, the fabricated nanoparticles wurtzite crystal structure was verified. Moreover, Fourier transform infrared (FT-IR) analysis verified the existence of functional groups in the fabricated nanoparticles. The migration of electrons from the deep donor level and zinc interstitial to the Zn-defect and O-defect is related to the emission peaks seen at 468, 480, 534, and 450 nm in photoluminescence (PL) spectra. Co-ZnO nanoparticles demonstrated potent and excellent photocatalytic degradation performance for TC (91.09%), AMP (87.97%), and AMX (92.42%) antibiotics within 210, 180, and 150 min of visible light irradiation. Co-ZnO nanoparticles also demonstrated strong antimicrobial performance against Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Aspergillus flavus, Aspergillus niger, and Bacillus subtilis. Further investigation of in vitro cytotoxic potential against the A549 cell line (IC50 = 24 ± 0.5 μg/mL) utilizing MTT assay and the free radical scavenging performance of Co-ZnO nanoparticles estimated by DPPH assay utilizing l-ascorbic acid as a reference was also performed. Anti-inflammatory potential is also reviewed by comparing it with the standard drug Diclofenac, and the maximum activity was obtained for Ni-ZnO nanoparticles (IC50 = 72.4 μg/mL).

Spatial patterns in the diet of Gyps vultures in India and their implications for conservation

Dietary analyses are particularly useful for developing conservation programmes for species threatened by resource depletion, poisoning and environmental pollution. Gyps vultures in South Asia represent one such case, having undergone a population collapse caused by feeding on carcasses of cattle treated with the non-steroidal anti-inflammatory drug diclofenac. Following a ban on the veterinary use of diclofenac, populations of vultures remain low and mostly concentrated near protected areas. Understanding the role of protected areas in the recovery of these critically endangered species requires analyses of spatial variation in their diet. We used faecal metabarcoding to investigate the spatial variation in the diet of Gyps vultures across four landscapes from sites located inside and outside protected areas. We collected faecal 642 samples, of which 419 yielded adequate molecular data to identify the vulture species and 30 molecular operational taxonomic units corresponding to at least 28 diet species. The diet was dominated by large ungulates and varied across landscapes, protection status and vulture species, with the observed variation largely explained by differential intake of wild and domestic species. Domestic livestock was present in >95 % of the samples from Central, West and North India, but 77 % of the samples had only wild species in South India. This variation was explained by livestock density within 100 km radius of the sampling site. Our results imply that protected areas may not offer a respite from possibility of diclofenac-poisoning across most parts of the country and efforts should continue unabated to remove nephrotoxic drugs from veterinary use.

Design, synthesis of new 2,4-thiazolidinediones: In-silico, in-vivo anti-diabetic and anti-inflammatory evaluation

In this study, a series of nine novel heterocyclic compounds were synthesized through a concise three-step reaction process. The synthesis involved Knoevenagel condensation at the 5th position of the 2,4-thiazolidinedione or rhodanine ring-system. Comprehensive physicochemical and spectral analyses, including FTIR, Mass, 1H NMR and 13C NMR, were performed to characterize the synthesized compounds. The synthesized derivatives were subjected to evaluation for their potential in various therapeutic domains. In-vivo anti-diabetic activity was assessed diabetes induced wistar rats, anti-inflammatory effects were gauged using the carrageenan and formalin induced rat paw edema model. Additionally, the in-vitro PPAR-γ modulatory activity, glucose uptake by using Saccharomyces cerevisiae and rat hemidiaphragm and cyclooxygenase inhibitory activity along with scavenge free radicals was tested by FRAP and DPPH method. According to the potential binding patterns of the most potent anti-diabetic compounds, namely 7a and 13a with the active sites of target PPAR-γ (PDB ID: 5U5L), was obtained through molecular docking using Schrodinger’s Glide model. Among the tested compounds, the compound 13a demonstrated significant antidiabetic activity with reduction in blood glucose levels (108.5 ± 2.171 mg/dL), comparable to the effect of pioglitazone (101.66 ± 0.95 mg/dL), similarly anti-inflammatory activity at fourth hour paw volume 93.6% and thickness at 3.99 ± 0.076 mm, respectively closer to that of standard drug diclofenac sodium (91.2% and 4.7 ± 0.057 mm) in carrageenan-induced paw edema in rat. The compound 13a displayed promising COX-2 inhibitory activity (IC50 = 7.82 μM) and DPPH antioxidant activity showcasing its multifaceted therapeutic potential. This study not only presents multi-targeting approach and highlights the significant potential compounds as a lead molecule for further therapeutic development.