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The novelty of this work is the simultaneous analysis of sulbactam (SUL), ampicillin (AMP), and paracetamol (PARA) in human urine samples, using the environmentally benign RP-HPLC method. A C18 column was used in chromatographic separation using potassium dihydrogen phosphate (10 mmol L–1, pH 5)/ethanol (90 %, V/V) as the mobile phase; flow rate was 1.00 mL min–1. UV detection at 220 nm was used for quantification. The proposed method showed good linearity in the concentration ranges of 2.20–250.00 μg mL–1 for SUL, 2.50–250.00 μg mL–1 for PARA, and 14.50–250.00 μg mL–1 for AMP. Direct injection of urine samples with no prior extraction was performed. This method was found successful in moving towards greener studies of drugs’ urinary excretion, by decreasing hazardous solvent consumption and waste. Moreover, the method was applied to investigate the urinary excretion of the drugs and possible interaction between ampicillin and paracetamol.

The correction notice in the journal "Pharmaceutics" addresses an error in Figure 6 of the original publication, which was a duplication of Figure 5. The correction involved repeating the flow cytometry experiment to ensure data accuracy and updating the machine used for Annexin-V FACS analyses. The authors confirm that the scientific conclusions remain unchanged, and the corrected version of Figure 6 is provided in the document. [Extracted from the article]

The aim of this study was to investigate the stability of three major antioxidants of Nigella sativa: thymoquinone (TQ), carvacrol (CR) and thymol (THY), under different stress conditions using HPLC and LC-MS/MS. Forced degradation for each compound was performed under different conditions, including oxidation, hydrolysis, photolysis and thermal decomposition. The results showed that both CR and THY were stable under the studied conditions, whereas TQ was not affected by acidic, basic and oxidative forced conditions but the effect of light and heat was significant. The degradation products of TQ were further investigated and characterized by LC-MS/MS. HPLC-UV method has been fully validated in terms of linearity and range, the limit of detection and quantitation, precision, selectivity, accuracy and robustness. The method was successfully applied to quantitative analysis of the principal antioxidants of Nigella sativa TQ, CR and THY in different phytopharmaceuticals.

Gastric ulcer is one of the most frequent gastrointestinal ailments worldwide. Indomethacin, one of the most potent NSAIDs, suffers undesirable ulcerogenic activity. Caffeic acid phenethyl ester (CAPE) has known health benefits. The current study examined the potential of CAPE to combat indomethacin-induced gastric ulcers in rats. Animals were randomized into 5 groups: control, Indomethacin (50 mg/kg) mg/kg), Indomethacin + CAPE (5 mg/kg/day), Indomethacin + CAPE (10 mg/kg), and Indomethacin + Omeprazole (30 mg/kg). CAPE prevented the rise in ulcer index, attenuated histopathological changes and preserved gastric mucin concentration. CAPE efficiently significantly prevented accumulation of malondialdehude (MDA) and prevented exhaustion of the enzymatic activities of catalase (CAT) and superoxide dismutase (SOD). Further, CAPE prevented the rise in the expression of tumor necrosis factor-α (TNF-α), cyclo-oxygenase-2 (COX-2) and nuclear factor kapp-B (NFκB). This was associated with down-regulation of Bax and up-regulation of Bcl-2 mRNA. Finally, CAPE prevented induced indomethacin-induced decrease in heat shock protein 70 (HSP70) in gastric tissues. In conclusion, CAPE possesses the ability to prevent indomethacin-induced gastric ulcer in rats. This involves, at least partially, antioxidation, anti-inflammation, anti-apoptosis and enhancement of HSP70 expression. [ABSTRACT FROM AUTHOR]

Andrographolide (AG), a major active constituent of Andrographis paniculata, is known to hinder proliferation of several types of cancer cells. However, its poor solubility and cellular permeability restrict its use in clinical applications. In this study, AG-loaded phytosomes (AG-PTMs) were formulated and optimized with respect to particle size using l-α-phosphatidylcholine (PC):AG ratio and sonication time (ST) as independent variables. The optimized formula was prepared at 1:2.7 for AG:PC molar ratio and 4.9 min for ST and exhibited a particle size of 243.7 ± 7.3 nm, polydispersity index (PDI) of 0.310 and entrapment efficiency of 72.20 ± 4.53. Also, the prepared formula showed a slow release of AG over 24-h period. The antiproliferative activity of AG-PTMs was investigated against the liver cancer cell line HepG2. AG-PTMs significantly repressed the growth of HepG2 cells with an IC50 value of 4.02 ± 0.14 µM. AG uptake by HepG2 cells was significantly enhanced in incubations containing the optimized formula. AG-PTMs also caused G2-M cell cycle phase arrest and increased the fraction of apoptotic cells in pre-G1 phase. These effects were associated with induction of oxidative stress and mitochondrial dysfunction. In addition, AG-PTMs significantly upregulated mRNA expression of BAX and downregulated that of BCL2. Furthermore, AG-PTMs significantly enhanced the concentration of caspase-3 in comparison to raw AG. These data indicate that the phytosomal delivery of AG significantly inhibited HepG2 cell proliferation through enhanced cellular uptake, arresting cell cycle at the G2-M phase and inducing mitochondrial-dependent apoptosis. [ABSTRACT FROM AUTHOR]

A new series of benzimidazole-1,2,3-triazole hybrids have been successfully accomplished by the Click chemistry of different aromatic azides and propargylated benzimidazole (4). The structural confirmations of the molecules were done by NMR, mass spectrometry, IR, and other techniques. All the newly synthesized compounds were tested for their antibacterial potentialities against two Gram-positive and two Gram-negative bacterial strains. The antibacterial results displayed comparable activity of two compounds (7) and (9) with the standard drug against S. aureus and S. epidermidis. The anticancer results showed that compounds (6, 7, 10, and 14) were more promising than tamoxifen toward MCF-7 cells. Whereas, compound (6) was the most potent molecule with IC50 3.23, 6.56, and 5.35 μM toward MCF-7, HepG2, and HCT-116 cell lines, respectively. The molecular docking showed that the synthesized molecules 6, 7, 10, and 14 with promising cytotoxicity displayed similar interaction like erlotinib with EGFR protein. These results suggest that these benzimidazole derivatives are promising lead molecules for chemotherapeutics and microbial infections. [ABSTRACT FROM AUTHOR]

Structural changes of small-molecule drugs may bring interesting biological properties, especially in the field of kinase inhibitors. We sought to study tirbanibulin, a first-in-class dual Src kinase (non-ATP competitive)/tubulin inhibitor because there was not enough reporting about its structure–activity relationships (SARs). In particular, the present research is based on the replacement of the outer ring of the biphenyl system of 2-[(1,1′-biphenyl)-4-yl]- N -benzylacetamide, the identified pharmacophore of KX chemotype, with a heterocyclic ring. The newly synthesized compounds showed a range of activities in cell-based anticancer assays, agreeing with a clear SAR profile. The most potent compound, (Z)- N -benzyl-4-[4-(4-methoxybenzylidene)-2-methyl-5-oxo-4,5-dihydro-1 H -imidazol-1-yl]phenylacetamide (KIM-161), demonstrated cytotoxic IC50 values at 294 and 362 nM against HCT116 colon cancer and HL60 leukemia cell lines, respectively. Profiling of this compound (aqueous solubility, liver microsomal stability, cytochrome P450 inhibition, reactivity with reduced glutathione, and plasma protein binding) confirmed its adequate drug-like properties. Mechanistic studies revealed that this compound does not depend on tubulin or Src kinase inhibition as a factor in forcing HL60 to exit its cell cycle and undergo apoptosis. Instead, KIM-161 downregulated several other kinases such as members of BRK, FLT, and JAK families. It also strongly suppresses signals of ERK1/2, GSK-3α/β, HSP27, and STAT2, while it downregulated AMPKα1 phosphorylation within the HL60 cells. Collectively, these results suggest that phenylacetamide-1 H -imidazol-5-one (KIM-161) could be a promising lead compound for further clinical anticancer drug development. [ABSTRACT FROM AUTHOR]