New Amino Acid Schiff Bases as Anticancer Agents via Potential Mitochondrial Complex I-Associated Hexokinase Inhibition and Targeting AMP-Protein Kinases/mTOR Signaling Pathway

Noser, Ahmed A.; Abdelmonsef, Aboubakr H.; El-Naggar, Mohamed; Salem, Maha M.

doi:10.3390/molecules26175332

Cited by 30 publications

(21 citation statements)

References 46 publications

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“…Flow cytometry was used to analyze cell cycle phases using an Accuri C6 flow cytometer (Becton Dickinson BD, Franklin Lakes, NJ, USA) on Caco cells 1 × 10 5 that were trypsinized, centrifuged at 5000 rpm at 4 • C, washed with cold phosphate buffer saline (PBS), and fixed with cold absolute ethanol, as described by Noser et al and Darzynkiewicz et al [80,81].…”

Section: Cell Cycle Examinationmentioning

confidence: 99%

Comparative LC–LTQ–MS–MS Analysis of the Leaf Extracts of Lantana camara and Lantana montevidensis Growing in Egypt with Insights into Their Antioxidant, Anti-Inflammatory, and Cytotoxic Activities

El-Din

Fahmy

et al. 2022

Plants

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Lantana camara L. and Lantana montevidensis Briq. (F. Verbenaceae) are invasive ornamental weeds native to the tropical regions of Africa and America. The leaves of both species have been traditionally used as infusions for treating fever, rheumatism, and cancer. LC–MS–MS-guided profiling of the methanolic extracts of the leaves of L. camara and L. montevidensis growing in Egypt led to the putative identification of 59 compounds belonging to terpenoids, flavonoids, iridoid glycosides, phenolic acids, and their derivatives. The in-vitro antioxidants and anti-inflammatory and anticancer activities of the two extracts were investigated. L. camara and L. montevidensis inhibited DPPH• (IC50 = 34.01 ± 1.32 and 47.43 ± 1.74 µg/mL), ABTS+ (IC50 = 30.73 ± 1.42 and 40.37 ± 1.51 µg/mL), and superoxide anion (IC50 = 1.57 ± 0.19 and 1.31 ± 0.14 μg/mL) free radicals. A potent anti-inflammatory effect was observed for both species through the inhibition of elastase release in fMLF/CB-induced human neutrophils (IC50 = 2.40 ± 0.16 and 1.90 ± 0.07 μg/mL). The extracts showed significant cytotoxic activity against a panel of cancer cell lines with the most potent activity against Caco cells (IC50 = 45.65 ± 1.64 and 40.67 ± 1.52 µg/mL for L. camara and L. montevidensis, respectively). Western blotting supported by FACS analysis revealed that the extracts inhibited cancer cell proliferation, reduced metastasis, and induced apoptosis resulting in cell cycle arrest. This was achieved via increasing mRNA and protein expressions of p53 and GSK-3β as well as decreasing the expression of PI3K, Akt, and cyclin D1.

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Section: Cell Cycle Examinationmentioning

confidence: 99%

Comparative LC–LTQ–MS–MS Analysis of the Leaf Extracts of Lantana camara and Lantana montevidensis Growing in Egypt with Insights into Their Antioxidant, Anti-Inflammatory, and Cytotoxic Activities

El-Din

Fahmy

et al. 2022

Plants

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“…Critical threshold (Ct) values for target gene were normalized to that of GAPDH. The fold change in gene expression was calculated as described previously (Livak and Schmittgen 2001 ; Noser et al 2021 ).…”

Section: Methodsmentioning

confidence: 99%

Quercetin mitigates rheumatoid arthritis by inhibiting adenosine deaminase in rats

El-Said

Atta

Mobasher

et al. 2022

Mol Med

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Rheumatoid arthritis (RA) is a chronic inflammatory joint disease characterized by synovial proliferation and bone destruction. Adenosine deaminase (ADA) is a key inflammatory enzyme that increases joint stiffness and pain in RA. In this study, we evaluated the in-silico, and in vivo inhibitory effect of quercetin isolated from Egyptian Fenugreek on ADA enzyme activity. We also determined the combinatorial effect of quercetin on methotrexate mediated anti-inflammatory efficacy and toxicity. In-silico molecular docking was conducted and confirmed in an in vivo RA rat model. The results showed that the inhibition constant of quercetin on joint ADA by docking and in-vitro was 61.9 and 55.5 mM, respectively. Therefore, quercetin exhibits anti-inflammatory effect in a rat RA model as evidenced by reducing the specific activity of ADA in joint tissues, lower jaw volume, enhance body weight, downregulate ADA gene expression, reduce levels of RA cytokines interleukin-1β, interleukin-6, tumor necrosis factor-α, also, rheumatoid factor, C-reactive protein, and anti-cyclic citrullinated peptide RA biomarker levels. These findings demonstrate that the purified quercetin has a promising anti-inflammatory effect against RA disease through its inhibitory effects on the ADA enzyme. Furthermore, isolated quercetin improved the anti-inflammatory efficacy of methotrexate, reduced its toxic effects by increasing antioxidant enzymes and reducing oxidative stress.

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“…The cell lines were incubated with the selected compound at several concentrations (0–200 μM) and doxorubicin (DOX) as a standard chemotherapeutic drug (0–100 μM) for 48 h, and then, the viability of the cells was determined using the MTT assay (Gibco-BRL, New York, NY, USA). 30 , 31 …”

Section: Materials and Methodsmentioning

confidence: 99%

Newly Synthesized Pyrazolinone Chalcones as Anticancer Agents via Inhibiting the PI3K/Akt/ERK1/2 Signaling Pathway

et al. 2022

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A series of novel pyrazolinone chalcones 3–9 have been synthesized through the condensation of azo pyrazolinone derivatives with various aromatic aldehydes. Spectroscopic techniques and elemental analysis have both corroborated this. Furthermore, all compounds were screened in silico for their ability to inhibit cancer proliferation and metastasis by targeting the PI3K/Akt signaling pathway. This inhibitory pathway might be an efficient approach for the death of cancer cells, angiogenesis, and metastasis prevention. Our results indicated that only compound 6b was the top-ranked. It demonstrated the highest binding energies of −11.1 and −10.7 kcal/mol against the target proteins PI3K and Akt, respectively; thus, it was chosen for in vitro studies. Compound 6b exhibited the most effective cytotoxic impact against the Caco cell line with IC 50 of 23.34 ± 0.14 μM. Furthermore, it showed significant inhibition of PI3K/Akt proteins and oxidative stress, leading to elevated Bax and p53 expression, reduced Bcl –2 expression, and triggered cell cycle arrest at the sub-G0/G1 phase. Additionally, it showed significant downregulation of the Raf-1 gene, leading to ERK1/2 protein inhibition. These findings demonstrate that compound 6b obeyed Lipinski’s rule of five and might be used as a favored scaffold for cancer treatment by inhibiting proliferation and metastasis via inhibition of the PI3K/Akt and Raf-1/ERK1/2 signaling pathways.

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New Amino Acid Schiff Bases as Anticancer Agents via Potential Mitochondrial Complex I-Associated Hexokinase Inhibition and Targeting AMP-Protein Kinases/mTOR Signaling Pathway

Cited by 30 publications

References 46 publications

Comparative LC–LTQ–MS–MS Analysis of the Leaf Extracts of Lantana camara and Lantana montevidensis Growing in Egypt with Insights into Their Antioxidant, Anti-Inflammatory, and Cytotoxic Activities

Comparative LC–LTQ–MS–MS Analysis of the Leaf Extracts of Lantana camara and Lantana montevidensis Growing in Egypt with Insights into Their Antioxidant, Anti-Inflammatory, and Cytotoxic Activities

Quercetin mitigates rheumatoid arthritis by inhibiting adenosine deaminase in rats

Newly Synthesized Pyrazolinone Chalcones as Anticancer Agents via Inhibiting the PI3K/Akt/ERK1/2 Signaling Pathway

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