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A validated ultraperformance liquid chromatography-tandem mass spectrometry (UPLC–MS/MS) method was developed for the first-ever simultaneous analysis of neratinib, curcumin and internal standard (imatinib) using acetonitrile as the liquid–liquid extraction medium. On a BEH C18 (100 mm × 2.1 mm, 1.7 μm) column, the analytes were separated isocratically using acetonitrile (0.1% formic acid):0.002M ammonium acetate. The flow rate was set at 0.5 mL.min−1. The authors utilized multiple reaction monitoring-based transitions for the precursor-to-product ion with m / z 557.099 → 111.928 for neratinib, m / z 369.231 → 176.969 curcumin and m / z 494.526 → 394.141 for imatinib during the study. Validation of the method as per United States Food and Drug Administration requirements for linearity (5–40 ng mL−1), accuracy and precision, stability, matrix effect, etc. were investigated and were observed to be acceptable. Afterward, we evaluated the method for establishing its greenness profile by using two greenness assessment tools and found it green. Overall, a reliable green UPLC–MS/MS method was devised and used to estimate neratinib and curcumin in human plasma simultaneously. [ABSTRACT FROM AUTHOR]

The discovery of multi-targeted kinase inhibitors emerged as a potential strategy in the therapy of multi-genic diseases, such as cancer, that cannot be effectively treated by modulating a single biological function or pathway. The current work presents an extension of our effort to design and synthesize a series of new quinazolin-4-one derivatives based on their established anti-cancer activities as inhibitors of multiple protein kinases. The cytotoxicity of the new derivatives was evaluated against a normal human cell line (WI-38) and four cancer lines, including HepG2, MCF-7, MDA-231, and HeLa. The most active compound, 5d, showed broad-spectrum anti-cancer activities against all tested cell lines (IC50 = 1.94–7.1 µM) in comparison to doxorubicin (IC50 = 3.18–5.57 µM). Interestingly, compound 5d exhibited lower toxicity in the normal WI-38 cells (IC50 = 40.85 µM) than doxorubicin (IC50 = 6.72 µM), indicating a good safety profile. Additionally, the potential of compound 5d as a multi-targeted kinase inhibitor was examined against different protein kinases, including VEGFR2, EGFR, HER2, and CDK2. In comparison to the corresponding positive controls, compound 5d exhibited comparable activities in nanomolar ranges against HER2, EGFR, and VEGFR2. However, compound 5d was the least active against CDK2 (2.097 ± 0.126 µM) when compared to the positive control roscovitine (0.32 ± 0.019 µM). The apoptotic activity investigation in HepG2 cells demonstrated that compound 5d arrested the cell cycle at the S phase and induced early and late apoptosis. Furthermore, the results demonstrated that the apoptosis pathway was provoked due to an upregulation in the expression of the proapoptotic genes caspase-3, caspase-9, and Bax and the downregulation of the Bcl-2 anti-apoptotic gene. For the in silico docking studies, compound 5d showed relative binding interactions, including hydrogen, hydrophobic, and halogen bindings, with protein kinases that are similar to the reference inhibitors. [ABSTRACT FROM AUTHOR]

In the present work, we have examined the composition of phytochemicals in the ethanolic extract of Haloxylon persicum Bunge and its biological activities. The measurements of the biological activities included its antioxidant behavior; antimicrobial activities against pathogenic fungi, gram-positive, and gram-negative bacteria; and anticancerous activity against hepatocellular (HepG-2), lung (A-549), breast (MCF-7), and colon (HCT-116) cancer cells. The analysis of the chemical composition showed the highest preponderance of tannins and the lowest for flavonoids. There were wide variations in the antioxidant activities that were dependent on the measures used (scavenging of 2,2-Diphenyl-1-picrylhydrazyl free radical and superoxide radical anion, O· 2 -) compared to ascorbic acid or butylated hydroxyl anisole. The concentration of the extract needed to cause 50% growth inhibition varied about threefold among different cancer cells with HepG-2 being the most sensitive and A-549 the least. The test of the antimicrobial potential showed Candida albicans to be the most sensitive with no activity against Aspergillus fumigatus, Penicillium italicum, Streptococcus mutants, and Enterobacter cloacae. The measurement of the effect of extract on the liver and kidney markers in the rat serum revealed no change in the activities suggesting safety of the extract. Therefore, ethanolic extract of H. persicum Bunge need further investigation for its possible use in humans. [ABSTRACT FROM AUTHOR]

Purpose: To develop a sensitive and accurate ultra-performance liquid chromatography–tandem mass spectrometric (UPLC-MS) method for quantification of ramipril in human plasma. Methods: Ramipril was extracted from biological fluid using equal volumes of n-hexane and propanol (1:1, v/v), and then chromatographed in a suitable C18 column with methanol: 0.1 % HCOOH (4: 1, v/v) as mobile phase. Atorvastatin was used as an internal standard for the chromatographic separation and quantification. The method was validated according to the United States Food and Drug Administration guidelines for standard indices. Results: Ramipril was determined in the concentration range 0.05 and 1000 ng/mL the validation procedure exhibited a correlation coefficient of 0.9979 + 0.002 (p = 0.05). The studied drug was quantified with lower ceiling of 0.05 ng/mL, and showed an accuracy of 105.00 %. Conclusion: A sensitive UPLC-MS analytical method has been successfully developed for the quantification of ramipril in human plasma. This method can be applied efficiently for the quantification of ramipril in bioavailability and pharmacokinetic studies. [ABSTRACT FROM AUTHOR]

Hearing loss is the incapability to hear sound, either partially or fully. One potential natural remedy for hearing loss is the use of Carthamus tinctorius , commonly known as safflower, contains bioactive compounds, including flavonoids, phenolic acids, and terpenoids, which possess potent antioxidant and anti-inflammatory activities. This study uses network pharmacology to identify the potential therapeutic effects of these compounds on hearing loss. We identified 17 active compounds of C. tinctorius with favorable ADME properties through a litrature search. Potential targets for these compounds were found using databases like STITCH and Swiss Target Prediction, as well as the GeneCards database to retrieve hearing loss-related potential targets. A Venn diagram was drawn to determine shared targets, and GO enrichment and KEGG pathways analysis of 64 key targets were conducted DAVID database. Protein-protein interactions (PPIs) were analyzed via STRING database, and a compound-target-pathway network was created in Cytoscape. Molecular docking studies focused on one hub gene, namely, tumor necrosis factor (TNF) revealing that C. tinctorius 's compounds have high affinity for TNF, suggesting a potential therapeutic link to hearing loss. Finally, molecular dynamics simulations and calculations of binding free energy showed TNF_Beta Sitosterol and TNF_Campesterol were more stable than TNF_Cholesterol. Our findings indicate that C. tinctorius may have therapeutic potential for hearing loss by targeting key genes and pathways. However, further in-vivo and in-vitro studies are needed to confirm these findings and determine optimal treatment parameters.

Long non-coding RNAs (lncRNAs) have emerged as pivotal regulators of gene expression, contributing significantly to a diverse range of cellular processes, including apoptosis. One such lncRNA is NEAT1, which is elevated in several types of cancer and aid in cancer growth. However, recent studies have also demonstrated that the knockdown of NEAT1 can inhibit cancer cells proliferation, movement, and infiltration while enhancing apoptosis. This article explores the function of lncRNA NEAT1 knockdown in regulating apoptosis across multiple cancer types. We explore the existing understanding of NEAT1's involvement in the progression of malignant conditions, including its structure and functions. Additionally, we investigate the molecular mechanisms by which NEAT1 modulates the cell cycle, cellular proliferation, apoptosis, movement, and infiltration in diverse cancer types, including acute myeloid leukemia, breast cancer, cervical cancer, colorectal cancer, esophageal squamous cell carcinoma, glioma, non-small cell lung cancer, ovarian cancer, prostate cancer, and retinoblastoma. Furthermore, we review the recent studies investigating the therapeutic potential of NEAT1 knockdown in cancer treatment. Targeting the lncRNA NEAT1 presents a promising therapeutic approach for treating cancer. It has shown the ability to suppress cancer cell proliferation, migration, and invasion while promoting apoptosis in various cancer types., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests., (Copyright © 2023 Elsevier GmbH. All rights reserved.)