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In this study, we synthesized novel α,β-unsaturated 2-cyanoacetamide derivatives (1–5) using microwave-assisted Knoevenagel condensation. Characterization of these compounds was carried out using FTIR and 1H NMR spectroscopy. We then evaluated their in vitro antibacterial activity against both gram-positive and gram-negative pathogenic bacteria. Additionally, we employed in silico methods, including ADMET prediction and density functional theory (DFT) calculations of molecular orbital properties, to investigate these cyanoacetamide derivatives (1–5). Molecular docking was used to assess the binding interactions of these derivatives (1–5) with seven target proteins (5MM8, 4NZZ, 7FEQ, 5NIJ, ITM2, 6SE1, and 5GVZ) and compared them to the reference standard tyrphostin AG99. Notably, derivative 5 exhibited the most favorable binding affinity, with a binding energy of -7.7 kcal mol−1 when interacting with the staphylococcus aureus (PDB:5MM8), while also meeting all drug-likeness criteria. Additionally, molecular dynamics simulations were carried out to evaluate the stability of the interaction between the protein and ligand, utilizing parameters such as Root-Mean-Square Deviation (RMSD), Root-Mean-Square Fluctuation (RMSF), Radius of Gyration (Rg), and Principal Component Analysis (PCA). A 50 nanosecond molecular dynamics (MD) simulation was performed to investigate stability further, incorporating RMSD and RMSF analyses on compound 5 within the active binding site of the modeled protein across different temperatures (300, 305, 310, and 320 K). Among these temperatures, compound 5 exhibited an RMSD value ranging from approximately 0.2 to 0.3 nm at 310 K (body temperature) with the 5MM8 target, which differed from the other temperature conditions. The in silico results suggest that compound 5 maintained significant conformational stability throughout the 50 ns simulation period. It is consistent with its low docking energy and in vitro findings concerning α,β-unsaturated cyanoacetamides.Key insights from this study include: • The creation of innovative α,β-unsaturated 2-cyanoacetamide derivatives (1–5) employing cost-effective, licensed, versatile, and efficient software for both in silico and in vitro assessment of antibacterial activity. • Utilization of FTIR and NMR techniques for characterizing compounds 1–5.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used as analgesics, antipyretics, anti-clotting, and anti-inflammatory agents. One such NSAID, ketoprofen (KTP), is prescribed to treat pain, sprains, menstrual irregularities, osteoarthritis (OA), and rheumatoid arthritis (RA). By inhibiting cyclooxygenase, it halts prostaglandin synthesis. However, it exhibits significant side effects in humans and other living things. Herein, the chemical structure of KTP has been modified to search for improved chemical and medicinal effects. Density functional theory (DFT) has been employed for geometry optimization. Molecular docking and molecular dynamics (MD) simulations were conducted to investigate the binding affinity and stability of the protein-drug complex with prostaglandin synthase protein. ADMET predictions were carried out to calculate and compare the pharmacokinetic behavior of KTP and its new analogs. Spectral and chemical results support the structural conformation of the new analogs, all of which exhibit improved physicochemical, and binding properties compared to the parent drug. After a 100 ns MD simulation, the drugs remained tightly bound to the binding site of the receptor protein, showing significant interactions with shorter distances among the new analogs. The ADMET predictions confirmed better pharmacokinetic properties of novel analogs compared to KTP. The study compares several KTP metabolites using thermo-chemical, spectral, biological, and toxicological analysis. Results showed the reactivity and stability, with spectral data evaluating all KTP analogs. ADMET predicts that all KTP derivatives are less toxic and have better pharmacokinetic features than KTP. Most KTP analogs exhibit excellent oral bioavailability and significant analgesic, antipyretic, and anti-inflammatory functions. These findings support the potential use of these drugs in the future drugs.

It is essential to develop high salt-tolerant rice varieties in order to cultivate the salt-affected lands. In this study, Na+/H+ exchanger 1 (NHX1) gene isolated from Vigna radiata L. Wilczek was transferred in Bangladesh Rice Research Institute (BRRI) developed two indica rice genotypes BRRI Dhan28 and BRRI Dhan29 using in-planta approach for improvement of salinity tolerance. Embryonic axes of matured dehusked rice seeds were injured and co-cultivated with Agrobacterium strain harboring VrNHX1 gene and finally regenerated. GUS histochemical assay and PCR amplification of GUS-a and VrNHX1 were performed to confirm the transformation. Expression confirmation was done by semi-quantitative RT-PCR. Under salinity stress, transgenic lines showed higher chlorophyll, relative water content and decreased electrolyte leakage, proline content, lipid peroxidation level, and catalase enzyme activity which represent the better physiology than control plants. Moreover, under salinity stress (150 mM), transgenic lines exhibited superior growth and salt tolerant than non-transgenic plants.

Datura inoxia is a subshrub plant known for its toxicity which results from the presence of the tropane alkaloid scopolamine and hyoscyamine. Saccharides are one of the most important elicitors that can alter physiological and biochemical responses in plants. This study targeted to increase the production of secondary metabolites in Datura inoxia avoiding genetic alteration and processes using different nontoxic and biodegradable compounds, utilizing calli induced from Datura inoxia stems to observe the effects of mannitol and sorbitol on the production of the two major secondary metabolites, scopolamine and hyoscyamine. Methanolic extract of the whole plant and callus was used to examine the production of two secondary metabolites in Datura inoxia using HPLC in a qualitative and quantitative manner which revealed the increased production of scopolamine and hyoscyamine in calli. The addition of mannitol and sorbitol in the media had a negative effect on both the fresh and dry weight of the calli but production of scopolamine and hyoscyamine increased significantly. In-vitro anti-microbial assay of hyoscyamine against Escherichia coli ATCC25922 and Candida albicans resulted in total inhibition of both the microbes in concentrations as low as 200 µg/ml.

Na + -K + -2Cl-cotransporter 1 (NKCC1) plays an important role in intracellular ionic homeostasis and cell volume regulation in the brain. Pathological activation of brain NKCC1 is associated with many brain disorders, including ischemic stroke, traumatic brain injury, epilepsy, neonatal seizure and autism, suggesting NKCC1 as a potential drug target. Several preclinical and clinical studies used Bumetanide, one of the “loop” diuretic drugs, to inhibit brain NKCC1 activity in neurodevelopmental and neurological disorders. However, poor brain penetration and potent diuretic effect limit its use. Thereby, we selected 1930 compounds, each having the capacity to penetrate into the brain to unmask the best candidates that can act as potent inhibitors for NKCC1 to curb this problem. Molecular docking was performed using PyRx to determine the maximum binding affinities (ranging from −9.3 to 9.0 kcal/mol)among the compounds and the NKCC1 to finally lay out the four top ranked compounds. ADMET analysis revealed that all the four compounds are safer drug candidates and that none of them posed either AMES toxicity or carcinogenicity when filtered on toxicological properties. Selected top-ranked each four compounds along with control (Bumetanide) underwent molecular dynamics (MD) simulations for 100ns each to validate the docking interactions where all four compounds with pubchem CID: (71753382), Pubchem CID:(5740383), Pubchem CID: (71692222) and Pubchem CID: (3442850) are highly supported by root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), radius of gyration (Rg), SASA (Solvent accessible Surface Area) value and Hydrogen bond analysis. Thus, our in silico investigation exhibits all four compounds as potent inhibitors for NKCC1.

This paper addresses the modification of poly(dimethylsiloxane), i.e. PDMS, using plasma surface treatment and a novel application of the membrane created. A set of model compounds were analysed to determine their permeation through PDMS, both with and without plasma treatment. It was found that plasma treatment reduced permeation for the majority of compounds but had little effect on some compounds, such as caffeine, with results indicating that polarity plays an important role in permeation, as is seen in human skin. Most importantly, a direct correlation was observed between plasma-modified permeation data and literature data through calculation of membrane permeability (Kp) values suggesting plasma-modified silicone membrane (PMSM) could be considered as a suitable in vivo replacement to predict clinical skin permeation.