Publications by authors named "Nada S Ibrahim"

5 Publications

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Bee venom and its active component Melittin synergistically potentiate the anticancer effect of Sorafenib against HepG2 cells.

Bioorg Chem 2021 Sep 3;116:105329. Epub 2021 Sep 3.

Zoology Department, Faculty of Science, Cairo University, Giza 12613, Egypt. Electronic address:

There are current attempts to find a safe substitute or adjuvant for Sorafenib (Sorf), the standard treatment for advanced hepatocellular carcinoma (HCC), as it triggers very harsh side effects and drug-resistance. The therapeutic properties of Bee Venom (BV) and its active component, Melittin (Mel), make them suitable candidates as potential anti-cancer agents per-se or as adjuvants for cancer chemotherapy. Hence, this study aimed to evaluate the combining effect of BV and Mel with Sorf on HepG2 cells and to investigate their molecular mechanisms of action. Docking between Mel and different tumor-markers was performed. The cytotoxicity of BV, Mel and Sorf on HepG2 and THLE-2 cells was conducted. Combinations of BV/Sorf and Mel/Sorf were performed in non-constant ratios on HepG2. Expression of major cancer-related genes and oxidative stress status was evaluated and the cell cycle was analyzed. The computational analysis showed that Mel can bind to and inhibit XIAP, Bcl2, MDM2, CDK2 and MMP12. Single treatments of BV, Mel and Sorf on HepG2 showed lower ICthan on THLE-2. All combinations revealed a synergistic effect at a combination index (CI) < 1. Significant upregulation (p < 0.05) of p53, Bax, Cas3, Cas7 and PTEN and significant downregulation (p < 0.05) of Bcl-2, Cyclin-D1, Rac1, Nf-κB, HIF-1a, VEGF and MMP9 were observed. The oxidative stress markers including MDA, SOD, CAT and GPx showed insignificant changes, while the cell cycle was arrested at G2/M phase. In conclusion, BV and Mel have a synergistic anticancer effect with Sorf on HepG2 that may represent a new enhancing strategy for HCC treatment.
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http://dx.doi.org/10.1016/j.bioorg.2021.105329DOI Listing
September 2021

Computational studies and sever apoptotic bioactivity of new heterocyclic cyanoacrylamide based p-fluorophenyl and p-phenolic compounds against liver carcinoma (Hepg2).

Bioorg Chem 2021 Sep 5;114:105147. Epub 2021 Jul 5.

Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt. Electronic address:

An efficient route for the preparation of new heterocyclic cyanoacrylamides based p-fluorophenyl and p-phenolic compounds was depicted. All structures were confirmed based on the different spectral tools and elemental analyses. MTT assay for the novel synthesized series was performed against four different cell lines (A549, MCF7, Hepg2, and Wi38). Among all tested groups, the p-phenolic compound 10 (207.1 µg/ml) and the corresponding p-fluorophenyl derivative 6 (325.7 µg/ml) were selected for further simulation and molecular studies against liver carcinoma. Compounds 6 and 10 were investigated theoretically to different protein sets as (cdk2, Bcl2-xl, cIAP1-BIR3, and MDM2) and they illustrated different binding affinities. The computational studies and different molecular techniques (e.g. cell cycle analysis, DPA assay, relative gene expression, and ELISA assay) were utilized in this report.
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http://dx.doi.org/10.1016/j.bioorg.2021.105147DOI Listing
September 2021

Novel [l,2,4]triazolo[3,4-a]isoquinoline chalcones as new chemotherapeutic agents: Block IAP tyrosine kinase domain and induce both intrinsic and extrinsic pathways of apoptosis.

Invest New Drugs 2021 Feb 28;39(1):98-110. Epub 2020 Aug 28.

Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt.

Two novel chemotherapeutic chalcones were synthesized and their structures were confirmed by different spectral tools. Theoretical studies such as molecular modeling were done to detect the mechanism of action of these compounds. In vitro cytotoxicity showed a strong effect against all tested cell lines (MCF7, A459, HepG2, and HCT116), and low toxic effect against normal human melanocytes (HFB4). The lung carcinoma cell line was chosen for further molecular studies. Real-time PCR demonstrated that the two compounds upregulated gene expression of (BAX, p53, casp-3, casp-8, casp-9) genes and decreased the expression of anti-apoptotic genes bcl2, CDK4, and MMP1. Flow-cytometry indicated that cell cycle arrest of A459 was induced at the G2/M phase and the apoptotic percentage increased significantly compared to the control sample. Cytochrome c oxidase and VEGF enzyme activity were detected by ELISA assay. SEM tool was used to follow the morphological changes that occurred on the cell surface, cell granulation, and average roughness of the cell surface. The change in the number and morphology of mitochondria, cell shrinkage, increase in the number of cytoplasmic organelles, membrane blebbing, chromatin condensation, and apoptotic bodies were observed using TEM. The obtained data suggested that new chalcones exerted their pathways on lung carcinoma through induction of two pathways of apoptosis. Graphical abstract Novel chalcones were prepared and confirmed by different spectral tools. Docking simulations were done to detect the mechanism of action. In vitro cytotoxicity indicated a strong effect against different cancer cell lines and low toxic effects against normal human melanocytes (HFB4). The lung carcinoma cell line was chosen for further molecular studies that include Real-time PCR, Flow-cytometry, Cytochrome c oxidase, and ELISA assay. SEM and TEM tool were used to follow the morphological changes occurred on the cell surface.
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http://dx.doi.org/10.1007/s10637-020-00987-2DOI Listing
February 2021

Synthesis, Cytotoxicity and Molecular Docking Simulation of Novel bis-1,4-Dihydropyridines Linked to Aliphatic or Arene Core via Amide or Ester-Amide Linkages.

Mini Rev Med Chem 2020 ;20(9):801-816

Chemistry Department, Faculty of Science, Cairo University, Giza, Egypt.

Objective: Novel bis(1,4-dihydropyridine-3,5-dicarbonitrile) derivatives linked to aliphatic or aromatic cores via amide or ester-amide linkages were prepared and their structures were confirmed by several spectral tools.

Methods: The synthesis of novel N,N'-(alkanediyl)bis(2-(2-(3,5-dicyano-2,6-dimethyl-1,4-dihydropyridin- 4-yl)phenoxy)acetamide) by acid-catalyzed condensation of the bis-aldehydes with four equivalents of 3-aminocrotononitrile was reported.

Results: The structures of the synthesized compounds were confirmed by different spectral tools. The molecular docking stimulation studies indicated that the prepared compounds bind to the active site of cellular inhibitor apoptotic protein (cIAP1-BIR3). MTT assay for the novel bis(1,4-dihydropyridines) was performed on two different human cell lines (A549 and HCT116).

Conclusion: Compound 5a showed higher cytotoxic activity against A549. Compound 5d showed moderate activity against HCT116. The rest of compounds indicated lower or no activity against both cell lines.
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http://dx.doi.org/10.2174/1389557519666190919160019DOI Listing
January 2021

Molecular Studies on Novel Antitumor Bis 1,4-Dihydropyridine Derivatives Against Lung Carcinoma and their Limited Side Effects on Normal Melanocytes.

Anticancer Agents Med Chem 2018 ;18(15):2156-2168

Chemistry Department, Faculty of Science, Cairo University, Giza, Egypt.

Background: Cancer is a complex genetic disease which is characterized by an abnormal cell growth, invasion and spreading to other parts of the body. There are several factors that lead to cancer by causing DNA damage and the impairment of its repair. Treatment of cancer using the chemotherapeutic drugs have adverse side effects such as toxicity as they lose their specificity toward cancer cells and affect also normal cells. Moreover, the cancer cells can resist the chemotherapeutic agents and make them ineffective. For these reasons, much attentions have been paid to develop new drugs with limited side effects on normal cells and to diminish cancer resistance to drug chemotherapy. Recently, some 1,4-dihydropyridine derivatives were reported to act as Multi-Drug Resistance (MDR) modulators that inhibit p-glycoprotein which is responsible for the inability of drugs to enter the cancer cells. Also 1,4-DHPs have antimutagenic properties against chemicals via modulating DNA repair when studied on drosophila.

Objective: The objective of this study is the synthesis of bis 1,4-DHPs incorporating ester as well as ether linkages and evaluate the anticancer activity of new compounds for synergistic purpose. Different genetic tools were used in an attempt to know the mechanism of action of this compound against lung cancer.

Method: An efficient one pot synthesis of bis 1,4-DHPs using 3-aminocrotononitrile and bis(aldehydes) has been developed. The cytotoxic effect against human cell lines MCF7, and A549 cell lines was evaluated.

Results: All compounds exhibited better cytotoxicity toward lung carcinoma cells than breast cancer cells. With respect to lung carcinoma cell line (A549), compound 10 was the most active compound and the three other compounds 7, 8, and 9 showed comparable IC values. In case of breast cancer cell line (MCF7), the most active one was compound 7, while compound 8 recorded the least activity.

Conclusion: we have developed an efficient method for the synthesis of novel bis 1,4-dihydropyridine derivatives incorporating ester or ether linkage. All compounds showed better cytotoxicity results against A549 than MCF7, so that lung carcinoma cell line was chosen to perform the molecular studies on it. The results showed that all compounds (7, 8, 9 and 10) caused cell cycle arrest at G1 phase. The molecular docking study on CDK2 confirmed the results of cell cycle assay which showed good binding energy between the compounds and the active site of enzyme indicating the inhibition of the enzyme.
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http://dx.doi.org/10.2174/1871520618666181019095007DOI Listing
August 2019
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