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Intercalation and in‐situ polymerization of POPD within MMT was successfully accomplished using sonochemical technique. Montmorillonite/poly(o‐phenylenediamine) (MMT/POPD) nanocomposites (NCs) were checked for their antimicrobial activity against four bacterial strains. The antibacterial activity of MMT/POPD NCs was investigated against E. coli, S. aureus, P. aeruginosa and B. subtilisby broth micro‐dilution and agar well diffusion methods. Furthermore, the effective concentration (EC50) and minimum inhibitory concentration (MIC) of the NCs were also determined. Results clearly showed that the NCs had viable cell reduction capability and could act as potential antibacterial agents. [ABSTRACT FROM AUTHOR]

Borage oil that is extracted from (Borago officinalis Linn.) is a well-known medicinal plant having various medicinal benefits. In this work, an affordable, simple, reliable, rapid and easily accessible high-performance thin-layer chromatography (HPTLC) method was developed for the estimation of gamma-linolenic acid (GLA) in borage oil. HPTLC method employs thin-layer chromatography (TLC) aluminum plates precoated with silica gel (G60F254) as the stationary phase, and the mixture of hexane:toulene:glacial acetic acid (3:7:1, v/v/v) was used as the mobile phase. Densitometric analysis of the TLC plates was carried out at 200 nm. The developed method showed well-resolved spots with retention factor (R f) value of 0.53 ± 0.04 for GLA. Various experimental conditions like saturation time for chamber, solvent phase migration and width of the band were studied intensely for selecting the optimum conditions. The method validation was performed for parameters like linearity, accuracy, specificity and precision. The values of limit of detection and limit of quantification for GLA were found to be 0.221 and 0.737 μg/band, respectively. In nutshell, the developed HPTLC method was found to be highly sensitive for the estimation of GLA in the herbal oil samples and formulations. [ABSTRACT FROM AUTHOR]

KRASG12D are the most prevalent oncogenic mutations and a promising target for solid tumor therapies. However, its inhibition exhibits tremendous challenge due to the necessity of high binding affinity to obviate the need for covalent binders. Here we report the evidence of a novel class of Imidazo[1,2- a ]pyridine derivative as potentially significant novel inhibitors of KRASG12D, discovered through extensive ligand-based screening against 2-[(2 R)-piperidin-2-yl]-1 H -indole, an important scaffold for KRASG12D inhibition via switch-I/II (S-I/II) pocket. The proposed compounds exhibited similar binding affinities and overlapped pose configurations to 2-[(2 R)-piperidin-2-yl]-1 H -indole, serving as a reliable starting point for drug discovery. Comparative free energy profiles demonstrated that C4 [2-methyl-3-((5-phenyl-1H-1,2,4-triazol-3-yl)methyl)imidazo[1,2- a ]pyridine] effectively shifted the protein to a stable low-energy conformation via a prominent transition state. The conformational changes across the transition revealed the conformational shift of switch-I and II to a previously known off-like conformation of inactive KRASG12D with rmsd of 0.91 Å. These conformations were even more prominent than the privileged scaffold 2-[(2 R)-piperidin-2-yl]-1 H -indole. The representative structure overlay of C4 and another X-ray crystallography solved BI-2852 bound inactive KRASG12D revealed that Switch-I and II exhibited off-like conformations. The cumulative variance across the first eigenvalue that accounted for 57 % of the collective variance validated this on-to-off transition. In addition, the relative interaction of C4 binding showed consistent patterns with BI-2852. Taken together, our results support the inhibitory activity of [2-methyl-3-((5-phenyl-1H-1,2,4-triazol-3-yl)methyl)imidazo[1,2- a ]pyridine] by shifting active KRASG12D to an inactive conformation. [ABSTRACT FROM AUTHOR]

Xylanases have become increasingly significant due to their versatile applications in the food, paper, and pharmaceutical industries. Nevertheless, the current production of these enzymes relies on costly substrates, with estimates indicating that over 30% of the production expenses are attributed to these substrates. The objective of this study is to optimize the physico-chemical parameters for obtaining the maximum production of xylanase enzyme from Bacillus sp. MCC2212. The production conditions were statistically optimized using Plackett-Burman design (PBD) and Central Composite design (CCD). The significant variables identified through PB design including temperature, substrate to moisture ratio, MgSO 4 , peptone, tween 20, inoculum size, inoculum age, incubation time, and extracted xylan, were further optimized using the CCD approach. This optimization process revealed the most influential factors affecting xylanase production, with optimal conditions observed at a temperature, 35 °C; a substrate to moisture ratio, 1:1.75 g:mL; MgSO 4 , 1.1%; peptone, 1.5%; tween 20, 1.25%; inoculum size, 10 % (v/w); inoculum age, 20 h; an incubation time, 50 h; and crude xylan extracted from wheat bran at a concentration of 6% v/w. The R2 value of the model was found to be 0.9901, indicating its effectiveness. The optimized CCD model displayed a 1.84-fold greater xylanase production than the PB design approach. These findings suggest that wheat bran, a readily available agro-waste, could be a feasible alternative to the conventional substrate, beechwood xylan, for the production of xylanase enzyme with the possibility of achieving higher production levels optimized by using statistical design approach. [Display omitted] • Stimulation of enzymes titer using cost effective substrate. • SSF cycle, using agro-waste extracts. • Optimization of fermentation media via two stage statistical design approach. • Enzyme activity enhanced by 1.84 fold. [ABSTRACT FROM AUTHOR]

Background: Neurodegenerative disorders (NDs), primarily affecting the elderly, are marked by complex pathophysiological processes and are projected to become the second leading cause of death. Parkinson's disease (PD), one of the most common NDs, is characterized by motor impairments due to reduced dopamine levels in the substantia nigra (SN), a crucial midbrain region involved in motor control and reward mechanisms. PD also impacts cognitive functions, potentially leading to depression and sleep disturbances. Recent research highlights the importance of MAO-B inhibitors in PD management, as these enzymes play a critical role in regulating neurotransmitter levels by catalyzing the oxidative deamination of intracellular amines and monoamine neurotransmitters. Result: Computational virtual screening of several quinoline-based ligands against the target protein MAO-B (PDB ID: 1OJA) was performed using molecular docking simulation and ADMET studies to identify promising inhibitors for neurodegenerative disease treatment. The most active hit, Compound PA001, exhibited a MolDock score of − 207.76 kcal/mol. Subsequent investigation of 6-methoxy-2-(4-phenylpiperazin-1-yl)quinoline (Compound PA001) using molecular dynamics (MD) simulations with GROMACS revealed potent inhibition and significant interactions at key active site residues. MD simulations confirmed the stability of the Compound PA001-MAO-B complex under physiological conditions. Additionally, ADMET analysis demonstrated that Compound PA001 possesses favorable drug-like properties, including absorption, distribution, metabolism, excretion, and toxicity profiles. These findings underscore 6-methoxy-2-(4-phenylpiperazin-1-yl)quinoline (Compound PA001) as a promising candidate for developing new MAO-B inhibitors to treat neurodegenerative diseases. Conclusion: The research highlighted 6-methoxy-2-(4-phenylpiperazin-1-yl)quinoline (Compound PA001) as a promising MAO-B inhibitor, exhibiting strong binding affinity, stability, and desirable drug-like characteristics for the treatment of neurodegenerative diseases. Among the top ten molecules, Compound PA001 was selected for molecular dynamics (MD) simulation using GROMACS. The compound showed potent inhibition, significant interactions with key active site residues, and stable complex formation under physiological conditions. ADMET analysis further confirmed its favorable pharmacokinetic profile. [ABSTRACT FROM AUTHOR]