Cancer is considered one of the top global causes of death. Natural products have been used in oncology medicine either in crude form or by utilizing isolated secondary metabolites. Biologically active phytomolecules such as gallic acid and quercetin have confirmed antioxidant, anti-bacterial, and neoplastic properties. There is an agreement that microorganisms could mediate oncogenesis or alter the immune system. This research project aims to develop a novel formulation of co-loaded gallic acid and quercetin into nanoliposomes and investigate the efficacy of the free and combined agents against multiple cancerous cell lines and bacterial strains. Thin-film hydration technique was adopted to synthesize the nanocarriers. Particle characteristics were measured using a Zetasizer. The morphology of nanoliposomes was examined by scanning electron microscopy, Encapsulation efficiency and drug loading were evaluated using High-Performance Liquid Chromatography. Cytotoxicity was determined against Breast Cancer Cells MCF-7, Human Carcinoma Cells HT-29, and A549 Lung Cancer Cells. The antibacterial activities were evaluated against Acinetobacter baumannii, Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, and Staphylococcus aureus. Therapeutic formulas were categorized into groups: free gallic acid, free quercetin, free-mix, and their nano-counterparts. Findings revealed that drug loading capacity was 0.204 for the mix formula compared to 0.092 and 0.68 for free gallic acid and quercetin, respectively. Regarding the Zeta potential, the mix formula showed more amphiphilic charge than the free quercetin and free gallic acid formulas (P-values 0.003 and 0.002 receptively). On the contrary, no significant difference in polydispersity indices was reported. Lung cancerous cells were the most affected by the treatments. The best estimated IC50 values were observed in breast and lung cancer lines for the nano-gallic acid and co-loaded particles. The nano-quercetin formula exhibited the least cytotoxicity with an IC50 value of ≥200 μg/mL in both breast (MCF-7) and colorectal adenocarcinoma cell lines (HT-29) with no activity against the lung. A remarkable improvement in the efficacy of quercetin was measured after mixing it with gallic acid against the breast and lungs. The tested therapeutic agents exhibited antimicrobial activity against gram-positive bacteria. Nano-liposomes can either enhance or reduce the cytotoxicity activity of active compounds depending on the physical and chemical properties of drug-loaded and type of cancer cells.
Qualitative and Quantitative Content Determination of Macro-Minor Elements in Bryonia Alba L. Roots using Flame Atomic Absorption Spectroscopy Technique
23 April 2008 in Journal of Liquid Chromatography & Related Technologies
A capillary zone electrophoretic (CZE) method has been developed for the determination of gemifloxacin and lomefloxacin in pharmaceutical tablet formulations. The CZE separation was performed using a 75 µm×35 cm fused silica capillary under the following conditions: 25°C; applied voltage, 12 kV; 25 mM H3PO4‐NaOH running buffer (pH 8.5). The detection wavelength was 254 nm. Flumequine was used as internal standard. The method was suitably validated with respect to linearity, limit of detection and quantification, accuracy, precision, specificity, and robustness. The calibration was linear from 5 to 50 µg mL−1 for gemifloxacin and 10 to 60 µg mL−1 for lomefloxacin, and the limit of detection and quantification were 2.93, 4.91 µg mL−1, and 3.87, 8.93 for gemifloxacin and lomefloxacin, respectively. Recoveries ranging from 94.4–108.6% were obtained for both drugs. The method was successfully applied to the determination of gemifloxacin and lomefloxacin in pharmaceutical tablets. Excipients present in the tablets and degraded products from different stress conditions did not interfere in the assay.
7 July 2022 in Nucleosides, Nucleotides & Nucleic Acids
Because of their superior antibacterial and pharmacokinetic capabilities, many nucleoside-based esters show potential against microorganisms, and may be used as pharmacological agents to address multidrug-resistant pathogenic problems. In this study, several aliphatic and aromatic groups were inserted to synthesize various 5′-O-decanoyluridine (2–5) and 5′-O-lauroyluridine derivatives (6–7) for antimicrobial, in silico computational, pharmacokinetic and POM (Petra/Osiris/Molinspiration). The chemical structures of the synthesized uridine derivatives were confirmed by physicochemical, elemental, and spectroscopic analyses. In vitro antimicrobial screening against five bacteria and two fungi, as well as the prediction of substance activity spectra (PASS), revealed that these uridine derivatives have promising antifungal properties when compared to the antibacterial activities. Density functional theory (DFT) was used to calculate the thermodynamic and physicochemical properties. Molecular docking was conducted against lanosterol 14a-demethylase CYP51A1 (3JUV) and Aspergillus flavus (1R4U) and revealed binding affinities and non-covalent interactions with the target. Then, a 150 ns molecular dynamic simulation was performed to confirm the behavior of the complex structure formed by microbial protein under in silico physiological conditions to examine its stability over time, which revealed a stable conformation and binding pattern in a stimulating environment of uridine derivatives. The acyl chain {CH3(CH2)9CO-} and {CH3(CH2)10CO-} in conjunction with sugar, was determined to have the most potent activity against bacterial and fungal pathogens in a structure-activity relationships (SAR) investigation. POM analyses were conducted with the presence of an antifungal (O δ− –- O’ δ−) pharmacophore site. Overall, the present study might be useful for the development of uridine-based novel multidrug-resistant antimicrobial. Graphical Abstract