Objective: The objective of this study was to design, synthesize, and evaluate the antibacterial efficacy of a novel library of hybrid heterocycles structuralized around a bio-sourced, O-alkylated vanillin framework to expand the chemical space of available antimicrobial agents. Methods: O-Alkylated vanillin (I) was functionalized through two divergent synthetic pathways. First, Knoevenagel condensation of I with diverse active methylene heterocycles yielded ylidene derivatives (II–V). Second, condensation of I with thiosemicarbazide afforded thiosemicarbazone (VI), which subsequently underwent regioselective cyclization with various active halo-compounds to generate thiazole derivatives (VII–IXa–IXe). Semicarbazone analogue (X) was synthesized using an optimized base-catalyzed method to evaluate comparative reactivity. All newly synthesized hybrids were evaluated in vitro for their antibacterial activity against Gram-positive (Staphylococcus aureus, Bacillus cereus) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) strains via the agar diffusion assay. Results and Discussion: A library of novel vanillin-centered hybrid heterocycles was successfully synthesized and structurally validated by IR and NMR spectroscopies. Chemical reactivity profiling revealed that while thiosemicarbazone VI readily underwent cyclization to form the corresponding thiazoles, the semicarbazone analogue X remained chemically refractory to cyclization under identical conditions. Antibacterial screening demonstrated potent, concentration-dependent inhibitory profiles across the synthesized derivatives. Notably, hybrid ylidene V, incorporating a thiazolo[3, 2-a]benzimidazol-3(2H)-one moiety, exhibited exceptional broad-spectrum antibacterial efficacy, consistently outperforming the other functionalized derivatives. Conclusions: Conjugating a bio-sourced vanillin core with tailored heterocyclic scaffolds provides a robust chemical strategy to enhance antimicrobial potency. The structurally optimized hybrid V represents a compelling lead candidate for the development of next-generation broad-spectrum antibacterial agents.

BACKGROUND:Rheumatoid arthritis (RA) is a long-term inflammatory disease linked to higher mortality, joint degeneration, and long-term disability. This study evaluated the anti-inflammatory, antioxidant, and immunomodulatory effects of Capsicum annuum (CAP) hydroethanolic extract and bee venom (BV) in Freund's complete adjuvant (FCA)-induced RA in rats. METHODS:Forty-eight rats were divided into six groups: normal control (NC), RA control, and RA groups orally treated with methotrexate (MTX) (0.25 mg/kg), CAP (100 mg/kg), BV (0.25 mg/kg), and CAP (100 mg/kg) + BV (0.25 mg/kg). RA was induced by intradermal injection of FCA (100 μL/rat) into a footpad of the right hind paw at two consecutive days, and treatments were administered for 3 weeks. The study assessed serum rheumatoid factor (RF), anticyclic citrullinated peptide (ACCP) antibodies (ACPAs), tumor necrosis factor-alpha (TNF-α), interleukin-4 (IL-4), oxidative stress markers such as lipid peroxidation, and antioxidant parameters including superoxide dismutase (SOD) and reduced glutathione (GSH). Additionally, mRNA expression of various genes (inducible nitric oxide synthase [iNOS], endothelial nitric oxide synthase [eNOS], interleukin-1β [IL-1β], TNF-α, matrix metalloproteinase-1 [MMP-1], matrix metalloproteinase-3 [MMP-3], and glutathione reductase [GR]) were analyzed, alongside histopathological evaluation. RESULTS:The data showed that CAP and/or BV significantly reduced serum inflammatory and oxidative stress biomarkers, enhanced the antioxidant defense system, and improved the histopathological changes of ankle joint. Gene expression analysis revealed downregulation of iNOS, eNOS, IL-1β, TNF-α, MMP-1, and MMP-3 gene expression, with upregulation of the GR gene expression. The combined CAP + BV treatment demonstrated the most potent antiarthritic effect. CONCLUSION:CAP and BV exhibit promising potential for alleviating RA in rats, with their combined application showing the greatest efficacy. The antiarthritic effects may be mediated via suppression of oxidative stress and inflammation and enhancement of the antioxidant defense system in addition to the modulatory effects on MMP-1 and MMP-3 gene expression. Further clinical research is essential to evaluate their safety and effectiveness in human RA management.

In this work, two oxazolidine derivatives 4 and 5 were conveniently prepared in high yields via the reaction of pseudoephedrine 1 with the corresponding bis(methythio)yledinenitriles 2 and/or 3, respectively using both ultrasonic and microwave irradiation techniques. The yields of oxazolidines 4 and 5 were summarized and compared with their preparation by traditional methods. X-ray diffraction analysis uncovers that a multitude of non-covalent interactions collaborate to establish the arrangement of crystals and the behavior of supramolecular assemblies in the solid state. The quantification of all intermolecular interactions is achieved through Hirshfeld surface analysis and fingerprint plots, while energy frameworks are constructed to examine the predominant energy interactions that contribute to the strength of molecular packing. In the experimental investigation, we conducted a thorough theoretical analysis employing quantum chemical techniques to ascertain the characteristics of the derivatives. The comparison of geometrical parameters revealed a strong agreement with the experimental findings. QTAIM has been used to analyze and characterize both covalent and non-covalent bonds. The closed-shell interactions at the bond critical point confirm the presence of non-covalent interactions.

Using one-pot multicomponent reactions, two new series of imidazoles (4a-o and 6a-d), were synthesized due to their great biological activity. The first series was accomplished by the reaction of O-alkyl vanillins 1a-c, ammonium acetate 2, and benzil derivatives 3a-e in ethanol, while the second series was obtained by reacting O-alkyl vanillins 1a, ammonium acetate 2, benzil 3a, and amino compounds (aniline 5a or amino acids 5b-d) in acetic acid. The in vitro antibacterial activity of the novel synthetic imidazoles was assessed against strains of gram positive bacteria, such as Bacillus cereus and Staphylococcus aureus, and gram negative bacteria, such as Pseudomonas aeruginosa and Escherichia coli. The findings indicated that some of the evaluated items have promising antibacterial agents, especially imidazoles 4d and 4e for (+G) bacteria and imidazoles 4c and 4f for (-G) bacteria.

In this study, a mixed sol-gel technique using silicate, polyvinyl alcohol (PVA), and polyethyleneimine (PEI) was used to various polymers based on PEI and silica gel. The c-PEI blend co-polymer was synthesized by cross-linking branching PEI in an aqueous solution with PVA. The produced c-PEI particles were highly positively charged and fit inside the range of tens to hundreds of nanometers of silica gel. It has been shown that the prepared c-PEI nanocomposite is a very effective antimicrobial, anti-inflammatory, and antioxidant material. In addition to the appropriate investigation of the anti-inflammatory activity using human red blood cells (HRBCs) stabilization, the developed materials were used to explore antimicrobial activity against yeast (Candida albicans ATCC-10231), Gram-negative bacterial strain (Escherichia coli ATCC-25922), and Aspergillus niger NRRL-3 as a fungus. FTIR, XRD, TEM, TGA, and DSC were among the biological and chemical methods used to characterize the produced c-PEI nanocomposites. The agar diffusion method was used to assess the biological activity of the synthesized compounds, and the results revealed a range in their in vitro-antimicrobial inhibitory activity. Based on the type of pathogenic microbe, the majority of the test substances showed a wide range of activity. The examined substances may be appropriate for the creation of an innovative antibacterial and antifungal medicinal medication.

A novel series of quinoxaline-1,3,4-oxadiazole derivatives was designed and synthesized as potential anticancer and anti-inflammatory agents. The anti-cancer activities were screened against HCT-116, HepG-2, MCF-7, and A549 cell lines, where compounds 3, 4d, 6, and 8 showed the highest activities against the tested cell lines. Mechanistically, compounds 3 and 4d exhibited significant inhibition activity against EGFR, with IC50 values of 0.093 and 0.107 mu M, respectively. On the other hand, compounds 4d and 8 demonstrated the strongest antiinflammatory activity, with IC50 of 1.912 and 2.1491 mu M, respectively, against COX2, indicating a mild selectivity toward COX2 over COX1. In addition, compound 4d was screened for its in vivo anti-inflammatory efficacy and showed a similar level of edema inhibition as celecoxib. Compound 4d arrested the growth of tumor cells at the G1/S phase. Furthermore, compound 4d primarily triggered cell death by stimulating early and late apoptosis. The molecular docking analysis conducted on EGFR and COX-2 enzymes demonstrated favorable binding modes 4d which is in consistent with the biological findings.

The protective potentials of Tribulus terrestris (TT) and L-arginine (L-Arg) against reproductive toxicity induced by fipronil (FPN) in male rats were investigated. A total of 36 male rats were allocated into six groups: control, TT, L-Arg, FPN, FPN + TT, and FPN + L-Arg groups. The body and sex organ weights, semen criteria, serum testosterone levels, and testicular oxidative stress were determined. Sexual behavior, testicular and penile androgen receptor (AR), penile nitric oxide synthase (NOS), immunohistochemistry of proliferating cell nuclear antigen (PCNA), and histopathology were also assessed. FPN disrupted reproductive health by influencing the expression and activity of NOS and AR, leading to compromised erectile function, sexual dysfunction, and hormonal imbalance. Significant improvements in body weight, reproductive organ weights, the expression of NOS and AR, and testosterone levels were observed in the TT- and L-Arg-treated groups. Behavioral assessments indicated improved sexual performance in the TT- and L-Arg-treated groups. Histopathological studies of the testes and penis tissue, immunohistochemical expression of PCNA in testicular tissues, and biochemical analyses further confirmed the protective effects of TT and L-Arg. Collectively, these findings highlighted the potential of TT and L-Arg in counteracting FPN-induced reproductive impairments.

: In this work, we synthesized a novel arylidene malononitrile 3 via the treatment of o -alkyl vanillin derivative 1 with malononitrile 2 in the presence of triethylamine (TEA) as a catalyst. The arylidene malononitrile 3 was subjected to react under one-pot multicomponent reaction (MCR) condition with respective methylarylketones 4a-f and sodium ethoxide 5 in ethanol to afford a new series of 2-(4-(6-aryl-3-cyano-2-ethoxypyridin-4-yl)-2-methoxyphenoxy)- N -phenylacetamides 6a-f . The structure of the new products was assured via spectral and elemental analysis. The reaction mechanism was suggested.

Two new pyrazolidine-3,5-dione derivatives were synthesized and their structures were elucidated by single-crystal X-ray analysis. The molecules were screened for their medicinal potential based on physiochemical and pharmacokinetics.

With the facile condensed carbonyl gourp of 2-hydorxybenzaldehyde with the amino group of quinoxalyl-2carbohydrazide, a new chelating quinoxalyl hydrazone derivative ligand (H 2 Lpx) was constructed. Its coordination behavior towards three divalent Co 2 + , Ni 2 + , and Cu 2 + ions was discovered by building up three new metallo-organic complexes (CoLpx, NiLpx, and CuLpx, respectively). Confirmation of their chemical structure was formulated by applying different spectroscopic methods, as well as, the micro-elemental (C,H,N) and thermogravimetric analyses, the conductance, and magnetic evaluations. The inhibition behavior of the free ligand and its metallo-organic complexes against the cell growth of six entitled microorganisms (three fungal and three bacterial types) and three tumors of humans was estimated considering the effective role of the divalent metal ions (Co 2 + , Ni 2 + , and Cu 2 + ions in their metallo-organic complexes). The interacting nature of H 2 Lpx, CoLpx, NiLpx, and CuLpx, with calf thymus DNA ( ct DNA) was manifested within the viscometric, spectrophotometric titrations and gel electrophoresis. The three complexes (CoLpx, NiLpx, and CuLpx) exposed a respectable inhibition attitude more than that of H 2 Lpx depending on the inhibition zone areas of the microbial series growth in mm and the half-inhibition concentration in mu M ( IC 50 ) for the tumor cell lines ' growth. Establishing of the interacted modes between H 2 Lpx and MLpx with ct DNA was built upon the shifts of the spectral scans for their solutions. In addition, chromism type, Gibb ' s free energy, and binding constant values ( Delta G /= b and K b , respectively) helped to distinguish their interacted modes, which supported DNA damage. The bio -action of MLpx complexes was highly modified compared to that of H 2 Lpx towards ct DNA.

AbstractNovel nanocomposites of polypyrrole (PPy) embedded in silica (SiO2) and iron phosphorus trisulphide (FePS3) nanoparticles have been fabricated. The nanocomposite's dielectric characteristics have been examined in relation to temperature ranges of 25–200°C and frequency ranges of 0.1–7 MHz. Fourier‐transform infrared spectroscopy (FTIR), x‐ray diffraction (XRD), scanning electron microscopy (SEM–EDX), transmission electron microscope (TEM), and dielectric measurements have all been used to evaluate the prepared nanocomposite. The monoclinic crystal structure of the prepared FePS3 and PPy/SiO2/FePS3 nanocomposite is confirmed by XRD, EDX, and TEM studies. The FePS3 is perfectly layered structure in the SEM image, and FePS3 and SiO2 particles are well intercalated, creating novel nanocomposites of two nanoparticle phases that served as a union network during the polymerization process. The IR spectrum shows that PPy is a dopant in the interlayer area of FePS3. The splitting major peak (570 cm−1) of FePS3 is visible at around 640 and 560 cm−1. The high AC conductivity values indicated that the combination of FePS3/SiO2 nano‐matrix contains PPy at high packing densities and confirming the semiconducting properties of the nanocomposite to be used in several electronic applications.

Dendrocalamus strictus Munro is a recognized medicinal plant, but research on its phytochemical and biological activity is limited. The research aims to explore the phytochemical and biological characteristics of the plant, especially antibiofilm, antioxidant, and cytotoxic effects. LC–ESI–MS/MS was utilized for the metabolic profiling of Dendrocalamus strictus. Total phenol and flavonoid contents were evaluated using Folin–Ciocalteu and aluminum chloride reagents, respectively. Antimicrobial activity, minimum inhibitory concentration (MIC), minimum biofilm inhibitory concentration (MBIC), and minimum biofilm eradication concentration (MBEC) were assessed. Free radical scavenging activity against DPPH was determined. The cytotoxic effects on several cell lines were examined using an MTT assay. Additionally, molecular docking was employed to assess tricin and isoorientin's antimicrobial and cytotoxic potential. Fourty seven components were identified, tricin is the most prominent (18.16

A novel series of cyanopyridines 7a-j were synthesized via a one-pot multicomponent reaction of arylidene 4 with ammonium acetate 5 and respective methylaryl/heterylketones 6a-j in ethanol using vanillin as a natural starting material. Moreover, the regioselective alkylation reaction was studied by the treatment of cyanopyridines 7a-f and 7j with CH3I in the presence of K2CO3 in DMF to afford O-methylcyanopyridines 8a-g (major) and N-methylcyanopyridines 9a-g (minor), whereas bipyridine 7h gave bipyridinium iodide salt 10. All of the designed cyanopyridines were evaluated as anti-breast cancer (MCF-7) cell lines via PIM Kinase inhibitory activity, and the results displayed that some of them showed high activities, especially compounds 7h and 8f, which showed excellent activities against MCF-7 with IC50 values of 1.89 and 1.69 μM, respectively, more potent than the reference drug doxorubicin. Mechanistically, compounds 7h and 8f exhibited strong in vitro PIM-1 kinase inhibitory activity with an IC50 of 0.281 and 0.58 μM, respectively, compared to the reference staurosporine. Moreover, compound 7h arrested the tumor cells at the S phase and caused cell death mainly by inducing early and late apoptosis. Molecular docking studies against PIM-1 revealed good binding modes of the synthesized compound and showed agreement with the biological results.

Both epigenetics and microbiomics are often considered to fall under the umbrella of 'post-genomics', as they challenge atomistic and static conceptions of organisms. In this chapter, we investigate how questions raised by epigenetics are also relevant for ethical questions surrounding the microbiome–gut–brain axis. We look at the idea that human beings are 'holobionts', and investigate how this matters for responsibility. We describe issues related to privacy and information in stool samples, and also the link between the human microbiome and mental health. We end by suggesting that, even more than epigenetics, microbiome research posits that human beings and other organisms are firmly entangled with, and partially defined by, the environment.

Novel nanocomposites of polypyrrole (PPy) embedded in silica (SiO2) and iron phosphorus trisulphide (FePS3) nanoparticles have been fabricated. The nanocomposite's dielectric characteristics have been examined in relation to temperature ranges of 25-200 degrees C and frequency ranges of 0.1-7 MHz. Fourier-transform infrared spectroscopy (FTIR), x-ray diffraction (XRD), scanning electron microscopy (SEM-EDX), transmission electron microscope (TEM), and dielectric measurements have all been used to evaluate the prepared nanocomposite. The monoclinic crystal structure of the prepared FePS3 and PPy/SiO2/FePS3 nanocomposite is confirmed by XRD, EDX, and TEM studies. The FePS3 is perfectly layered structure in the SEM image, and FePS3 and SiO2 particles are well intercalated, creating novel nanocomposites of two nanoparticle phases that served as a union network during the polymerization process. The IR spectrum shows that PPy is a dopant in the interlayer area of FePS3. The splitting major peak (570 cm(-1)) of FePS3 is visible at around 640 and 560 cm(-1). The high AC conductivity values indicated that the combination of FePS3/SiO2 nano-matrix contains PPy at high packing densities and confirming the semiconducting properties of the nanocomposite to be used in several electronic applications.

Quinoxaline represents one of the most important classes of heterocyclic compounds, which have exhibited a wide range of biological activities and industrial importance in many different fields. In this regard, we have synthetized two new quinoxaline derivatives. Their structures were confirmed by single-crystal X-ray analysis. The compounds show potent activity against adenosine receptors A2AAR based on structural activity relationship studies. Further molecular docking, molecular dynamics, ADMET analysis, and DFT (density functional theory) calculations were performed to understand the titled compound's future drug candidacy. DFT computations confirmed the good stability of the synthesized compounds, as evidenced by the optimized molecular geometry, HOMO-LUMO energy gap, and intermolecular interactions. NBO analysis confirmed intermolecular interactions mediated by lone pair, bonding, and anti-bonding orbitals. All DFT findings were consistent with experimental results, indicating that the synthesized molecules are highly stable. These findings suggest that the synthesized compounds are promising candidates for further development as drugs for the treatment of A2AAR-related diseases.

Methylene blue (MB) is a well-known dye that is used in many industries and is highly polluting to the environment. Therefore, this paper proposes using sunflower husks (SFH) through a coating with a nanomaterial made of silicon dioxide (SiO2) with a weight percentage (w/w) of 5:1 to produce (SFH-SiO2) nanoparticles for removing MB from aqueous solutions. This method, known as green synthesis, is characterized by being environmentally friendly and low-cost, as well as efficient in the removal process. The prepared composite was characterized by conducting analysis using Field emission scanning electron microscopy (SEM) with (EDX), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) were used to look at the samples. The optimal conditions for the removal process were found to be at a pH of 6, with 0.2 g/50 mL of dose adsorbent. At a temperature of 25 °C, the best time to remove the dye was 150 minutes. With a maximal adsorption capacity (qmax) of 70.16 mg g−1, the findings match the Freundlich model. The adsorption process follows a pseudo-second-order. The negative value of Gibbs free energy (ΔG°) indicated the reaction was spontaneous. (SFH-SiO2) nanoparticles could represent a suitable method for removing cationic dyes from aquatic environments.

Rheumatoid arthritis (RA) is an autoimmune illness affecting joint articulations, leading to a disability state. Currently, there is no satisfying optimal therapy except for immunosuppressants, which have variable and bad effects after long-term use. Hence, researchers have attempted to develop other alternative, safer, and more effective natural treatment agents that are effective and without undesirable effects. The objective of this research is to assess the antiarthritic properties of navel orange peel ethanolic extract (NOPEE) and naringin (NAR) in experimentally induced RA in male Wistar rats. RA was induced via two successive subcutaneous injections of 0.1 mL complete Freund's adjuvant (CFA) into a footpad of the right hind leg. The arthritic rats were orally treated with 100 mg/kg body weight (b.w.)/day of NOPEE or with 25 mg/kg b.w./day of NAR for 14 days. Results showed that treatment with NOPEE or NAR obviously counteracted the increased ankle joint circumference, inflammatory cell infiltration, pannus development, cartilage degradation, and synovial hyperplasia that developed in CFA-induced arthritic rats. Additionally, the elevation of serum rheumatoid factor (RF), prostaglandin E2 (PGE-2), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and interleukin-17 (IL-17) were significantly declined in parallel to enhanced level of serum interleukin-4 (IL-4). Furthermore, NOPEE and NAR supplementation, reversed the negative oxidative effects of lipid peroxidation (LPO), nitric oxide (NO), as well as improved the antioxidant glutathione level (GSH), glutathione reductase (GR) and superoxide dismutase (SOD) activities. Overall, the anti-arthritic effects of NOPEE and NAR may be mediated through their modulatory effects on T helper (Th)1/Th2/Th17 cytokines, oxidative stress, and the antioxidant defense system.

Pain produces several physiological, and degenerative complications. This study aimed to formulate meloxicam (MLX) in liposomes to increase solubility and deliver MLX in a controlled manner to overcome its poor aqueous solubility and relatively short t1/2 problems. Liposomes were prepared by thin film hydration followed by ultrasonication. Tests for characterizing formulations included particle size, span, entrapment efficiency, drug loading, stability, differential scanning calorimetry (DSC), Fourier transformation infrared (FT-IR) spectroscopy, morphology, in vitro release, release kinetics mathematical modeling, and an in vivo pain model in dogs undergoing orthopedic surgeries, followed by in vivo pharmacokinetics, pharmacodynamics, and pain assessment studies in comparison to the reference standard, Mobitil (R). Liposomal MLX had a particle size of around 100 nm, 82 % entrapment efficiency, and 4.62 % drug loading. Stability studies, DSC, and FT-IR spectroscopy indicated that liposomes were highly stable. The formulation showed an improved in vitro controlled release pattern and an enhanced in vivo pharmacokinetic behavior as manifested by higher t1/2 and AUC0-24 and lower Cl/F in comparison to Mobitil (R). The pharmacodynamics study and pain scales demonstrated liposomal MLX managed postoperative pain better than Mobitil (R). In conclusion, the incorporation of MLX in liposomes increased its solubility and stability, as well as its pain management properties.