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The rising instances of drug resistance in Mycobacterium tuberculosis strains pose a significant global health challenge. Conventional tuberculosis (TB) treatments, which typically involve multiple antibiotics, face hurdles like drug resistance, reduced effectiveness, and heightened toxicity. Consequently, there is a pressing need for innovative anti-TB agents with new modes of action. Decaprenyl-phosphoryl-β-d-ribose 2′-epimerase 1(DprE1), a crucial enzyme in Mycobacterium tuberculosis, plays a vital role in cell wall biosynthesis – a critical aspect for the bacterium’s survival. Building on the success of diarylquinolines like bedaquiline, targeting DprE1 presents a promising avenue for developing anti-TB drugs, especially against drug-resistant strains. Our research focused on discovering novel DprE1 inhibitors using a ligand-based drug design strategy, starting with the established non-covalent inhibitor Ty38c. We assembled a library of 16 molecules, modifying them based on factors like drug-like properties, chemical accessibility, and synthetic feasibility. Molecular docking analyses of this library identified three molecules with binding affinities comparable to Ty38c. Among these, KS_QD_05 and KS_QD_04 are promising candidates, which were further validated through molecular dynamics simulation studies where root-mean-square deviation (RMSD) values of all three complexes reached a plateau, measuring around 0.3 nm, indicating that the apoprotein and all complexes stabilized during the simulation. The ligands KS_QD_04 and KS_QD_05 displayed significantly stable deviation. KS_QD_05 reached about 0.1 nm equilibrium value. However, the ligand KS_QD_04 reached an RMSD value of 0.17 nm and showed distress at 70 nm. KS_QD_04 and KS_QD_05 showed an average value of 1-3 H-bond interaction and regarding the RMSF values, both the compounds showed fluctuations less than 0.5 nm in the case of Mtb. DprE1 enzyme. This indicates the potential of both compounds to become lead compounds in the pursuit of DprE1 inhibitors for TB treatment.

This research presents a straightforward, effective, and eco-friendly method for the production of silver nanoparticles (AgNPs) and copper oxide nanoparticles (CuONPs) using the dried fruit of Amomum subulatum as a reducing, stabilizing, and capping agent. The formation of AgNPs and CuONPs is supported by the presence of a surface plasmon resonance band (SPR) at 440 nm for AgNPs and 245 nm for CuONPs. Additionally, the identification of specific biomolecules responsible for the synthesis of AgNPs and CuONPs was confirmed through FTIR spectra analysis. The Transmission electron microscope (TEM) images demonstrated that AgNPs and CuONPs had spherical shapes, with mean particle diameters of 20.6 nm and 24.7 nm, respectively. X-ray diffraction and selected area electron diffraction (SAED) analyses provided evidence of the crystalline nature of the synthesized AgNPs and CuONPs. Additionally, the presence of silver and copper elements was observed through energy-dispersive X-ray spectroscopy (EDS) analysis. Furthermore, the antibacterial activity of AgNPs was found to be superior to that of CuONPs against human pathogens such as Escherichia coli, Staphylococcus aureus, and Bacillus subtilis. The cytotoxic activity of the biosynthesized nanoparticles (NPs) was evaluated in vitro against human cervical cells (HeLa) and human breast cells (MCF-7). In MCF-7 cells, the IC50 value for AgNPs was estimated to be 39.79 µg/mL, while that of CuONPs was 83.89 µg/mL. In HeLa cells, the IC50 value for AgNPs was 45.5 µg/mL, and for CuONPs, it was 97.07 µg/mL. For the first time, an eco-friendly method for the synthesis of AgNPs and CuONPs from fruit extract of Amomum subulatum has been discussed along with their comparative evaluation study. These results highlight the promising applications of the eco-friendly synthesized AgNPs and CuONPs as effective agents against microbial infections and potential candidates for cancer therapy. [ABSTRACT FROM AUTHOR]

Tramadol (TD) has been prescribed frequently in many countries for more than 40 years, but there is a risk of its misuse and trafficking. As a result, drug analysis has numerous legal and socially relevant implications, making it an essential part of modern analytical chemistry. Thus, the method for the detection of TD and its phase I and phase II metabolites in human urine has been developed and validated using a rapid and efficient approach combining liquid chromatography-tandem mass spectrometry (LC-MS/MS) with electrospray ionization. The sample preparation was best performed using dispersive liquid–liquid microextraction. Analysis was performed using an HyPRITY Cl8 column, and isocratic elution with methanol: water (35:65) with 0.2% formic acid was used. TD and its metabolites were detected at 264.2 (TD/M0) with a base peak at 58.2, 250.3758 (M1), 250.3124 (M2), 236.3976 (M3), 222.5361 (M4), and 236.4475 (M5) m/z peaks. TD showed linearity between 0.1 and 160 ng/mL (R2 = 0.9981). The accuracy ranged from 95.56 to 100.21% for the three concentration levels, while the between- and within-day RSD ranged from 1.58 to 3.92%. The absolute TD recovery was 96.29, 96.91, and 94.31% for the concentrations of 5, 50, and 150 ng/mL, respectively. TD's phase I metabolites, M1–5 along with nine phase II metabolites, such as sulfo- and glucurono-conjugated metabolites, oxidative TD derivatives, and sulfo-conjugated metabolites were also identified in the urine samples. The pharmacokinetics and metabolism data given provide information for the design of possible future research disorders, evaluating drug mechanism and neurotoxicity and for the effective application screening of TD. [ABSTRACT FROM AUTHOR]

The present study aims to enhance the bioavailability of Blueberry by formulating it as nanosuspension. Blueberry mainly consists of anthocyanins which have strong antihyperlipidemic activity but suffers from low bioavailability which causes hindrances in its therapeutic activity to treat hyperlipidemia. Hence to improve its bioavailability, nanosuspension of blueberry was prepared. Box-Behnken design was applied to predict the effect of independent variables namely concentration of chitosan and concentration of tripolyphosphate (TPP) and stirring speed on two responses namely particle size and entrapment efficiency. The design suggested that a formulation having a particle size of 205.05nm and entrapment efficiency of 76.60 % will be an optimized formulation if it has chitosan, TPP, and stirring speed of 0.5%, 0.05%, and 1050 rpm respectively. The formulation suggested by design was prepared and it was found that particle size and entrapment efficiency of nanosuspension 198.5 nm and 75.14±0.56 % respectively. In addition, it was found to have polydispersity index, refractive index, zeta potential of 0.351, 1.33, 21.08mv respectively.SEM analysis showed the droplet size under 200nm. When compared towards blueberry nanosuspension with drug extract release it shows the controlled release of drug up to 8 hrs which enhances the bioavailability of drug and drug extract suspension showed the maximum release in 2hrs which shows the immediate release of the drug. As a result, our research shows that nanotechnology might be utilized as an effective approach increasing the bioavailability of blueberry nanosuspension and this article also focuses on the antihyperlipidemic activity of anthocyanin. [ABSTRACT FROM AUTHOR]