Browsing by Author "Khaled, Azza M"

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Design, synthesis, in vitro urease inhibitory potentials and in silico molecular docking study of benzimidazole bearing thiosemicarbazides/ sulfonamide Analogues
(Elsevier, 2023-10) Alzahrani, Abdullah Yahya Abdullah; Adalat, Bushra; Ullah, Hayat; Taha, Muhammad; Othman, Mohamed S; Fareid, Mohamed A; Khaled, Azza M; Rahim, Fazal
The nickel-containing urease enzyme is responsible for the pathogenesis of hepatic coma, hepatic encephalop- athy, urolithiasis, gastric and peptic ulcer. These enzymes also have a negative effect on the efficacy of soil nitrogen to produce crops. The urease enzyme inhibitors may be thought as a strategy for reducing the negative effects of ureolytic bacteria. The present study involves a novel approach to the synthesis benzimidazole thio- semicarbazides and sulphonamide derivatives as potent urease inhibitor. All the analogues exhibited good in- hibition potential. Among the thiosemicarbazides series, the most potent were analogs 1 g and 1 h having an IC50 = 2.40 ± 0.10 and 3.10 ± 0.10 µM respectively. Among the sulphonamide series, the most potent analogs were 2f and 2j having an IC50 = 3.90 ± 0.10 and 1.40 ± 0.001 µM respectively. Structure activity relationship study shows that among the two series, the most potent analogs were those having electron-withdrawing groups. Molecular docking study was carried out to check the interactions between the synthesized compounds and the urease enzyme’s active sites. Furthermore, to evaluate the stability of the most active compound in complex with the urease enzyme a total of 200 ns MD simulation was carried out. The MD simulation study revealed that the compound formed a more stable complex with the urease enzyme and remained stable throughout the 200 ns MD simulation. All Compounds were verified for cytotoxicity against 3T3 mouse fibroblast cell line and detected nontoxic.
Green-Synthesized Silver and Selenium Nanoparticles Using Berberine: A Comparative Assessment of In Vitro Anticancer Potential on Human Hepatocellular Carcinoma Cell Line (HepG2)
(Multidisciplinary Digital Publishing Institute (MDPI), 2024-02) Khaled, Azza M; Othman, Mohamed S; Obeidat, Sofian T; Aleid, Ghada M; Aboelnaga, Shimaa M; Fehaid, Alaa; Hathout, Heba M. R; Bakkar, Ashraf A; Abdel Moneim, Ahmed E; El-Garawani, Islam M; Morsi, Dalia S
A well-known natural ingredient found in several medicinal plants, berberine (Ber), has been shown to have anticancer properties against a range of malignancies. The limited solubility and bioavailability of berberine can be addressed using Ber-loaded nanoparticles. In this study, we compared the in vitro cytotoxic effects of both Ber-loaded silver nanoparticles (Ber-AgNPs) and Ber-loaded selenium nanoparticles (Ber-SeNPs) in the human liver cancer cell line (HepG2) and mouse normal liver cells (BNL). The IC50 values in HepG2 for berberine, Ber-AgNPs, Ber-SeNPs, and cisplatin were 26.69, 1.16, 0.04, and 0.33 µg/mL, respectively. Our results show that Ber and its Ag and Se nanoparticles exerted a good antitumor effect against HepG2 cells by inducing apoptosis via upregulating p53, Bax, cytosolic cytochrome C levels, and caspase-3 activity, and the down-regulation of Bcl-2 levels. Similarly, incubation with Ber and both Ber-NPs (Ag and Se) led to a significant dose-dependent elevation in inflammatory markers’ (TNF-α, NF-κB, and COX-2) levels compared to the control group. In addition, it led to the arrest of the G1 cell cycle by depleting the expression of cyclin D1 and CDK-2 mRNA. Furthermore, Ber and both Ber-NPs (Ag and Se) caused a significant dose-dependent increase in LDH activity in HepG2 cells. Furthermore, our findings offer evidence that Ber and its nanoparticles intensified oxidative stress in HepG2 cells. Furthermore, the migration rate of cells subjected to berberine and its nanoforms was notably decreased compared to that of control cells. It can be inferred that Ber nanoparticles exhibited superior anticancer efficacy against HepG2 compared to unprocessed Ber, perhaps due to their improved solubility and bioavailability. Furthermore, Ber-SeNPs exhibited greater efficacy than Ber-AgNPs, possibly as a result of the inherent anticancer characteristics of selenium.
Hepatorenal protective efficacy of flavonoids from Ocimum basilicum extract in diabetic albino rats: A focus on hypoglycemic, antioxidant, anti-inflammatory and anti-apoptotic activities
(Elsevier, 2021-12) Othman, Mohamed S; Khaled, Azza M; Al-Bagawi, Amal H; Fareid, Mohamed A; Ghany, Reda A; Habotta, Ola A; Abdel Moneim, Ahmed E
Plant derived phytochemical therapy is a bright candidate for treatment of diabetes and its associated complications. Ocimum baslicum is used as an anti-diabetic traditional medicine. Hence, the present study investigated the effect of Hail Ocimum extract (HOE) and its total flavonoids (HOETF) against hepatorenal damage in experimental diabetes induced by high-fat diet (HFD) and injection of streptozotocin (STZ) in rats. Diabetic animals were co-treated daily with HOE, HOETF or metformin (MET) as a standard anti-diabetic drug for four weeks. Compared to controls, HFD/STZ-treatment lead to significant increases in fasting blood glucose, insulin and HOMA-IR levels. Furthermore, diabetic rats had elevated hepatic (ALT and ALP) and kidney functions (urea and creatinine) biomarkers together with disturbed lipid profile and decreased PPAR-γ gene expression. Higher levels of hepatic and renal LPO and NO paralleled with lower levels of GSH and activities of antioxidant enzymes (SOD, CAT, GPx and GR) after HFD/STZ treatment. Additionally, noteworthy inflammatory and apoptotic responses were evident in both organs of diabetic rats as witnessed by augmented levels of TNF-α, IL-1b and Bax levels with declined levels of Bcl-2. Moreover, histological examination of hepatic, renal and pancreatic tissues validated the biochemical findings. On contrary, co-treatment of diabetic animals with HOE or HOETF could decrease glucose and insulin levels together with improvement of lipid markers and alleviation of hepatorenal dysfunction, oxidative injury, inflammatory and apoptotic events. Conclusively, HOE or HOETF could be a promising complementary therapeutic option for the management of diabetic hepatorenal complication owing to their antioxidant, anti-inflammatory; anti-apoptotic properties.