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Your search keyword '"Elmeligie, Salwa"' showing total 3 results
Start Over Author "Elmeligie, Salwa" Topic drug design
3 results on '"Elmeligie, Salwa"'

1. Design and synthesis of phthalazine-based compounds as potent anticancer agents with potential antiangiogenic activity via VEGFR-2 inhibition.

Author

Elmeligie S, Aboul-Magd AM, Lasheen DS, Ibrahim TM, Abdelghany TM, Khojah SM, and Abouzid KAM

Subjects
Antineoplastic Agents chemical synthesis, Antineoplastic Agents chemistry, Cell Death drug effects, Cell Line, Tumor, Cell Proliferation drug effects, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Humans, Molecular Structure, Phthalazines chemical synthesis, Phthalazines chemistry, Protein Kinase Inhibitors chemical synthesis, Protein Kinase Inhibitors chemistry, Structure-Activity Relationship, Vascular Endothelial Growth Factor Receptor-2 metabolism, Antineoplastic Agents pharmacology, Drug Design, Phthalazines pharmacology, Protein Kinase Inhibitors pharmacology, Vascular Endothelial Growth Factor Receptor-2 antagonists & inhibitors
Abstract

In the designed compounds, either a biarylamide or biarylurea moiety or an N-substituted piperazine motif was linked to position 1 of the phthalazine core. The anti-proliferative activity of the synthesised compounds revealed that eight compounds ( 6b, 6e, 7b, 13a, 13c, 16a, 16d and 17a ) exhibited excellent broad spectrum cytotoxic activity in NCI 5-log dose assays against the full 60 cell panel with GI 50 values ranging from 0.15 to 8.41 µM. Moreover, the enzymatic assessment of the synthesised compounds against VEGFR-2 tyrosine kinase showed the significant inhibitory activities of the biarylureas ( 12b, 12c and 13c ) with IC 50 s of 4.4, 2.7 and 2.5 μM, respectively, and with 79.83, 72.58 and 71.6% inhibition of HUVEC at 10 μM, respectively. Additionally, compounds ( 7b, 13c and 16a) were found to induce cell cycle arrest at S phase boundary. Compound 7b triggered a concurrent increase in cleaved caspase-3 expression level, indicating the apoptotic-induced cell death.

Published
2019
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2. Design and Synthesis of Pyridazine Containing Compounds with Promising Anticancer Activity.

Author

Elmeligie S, Ahmed EM, Abuel-Maaty SM, Zaitone SA, and Mikhail DS

Subjects
Animals, Antineoplastic Agents chemistry, Cell Proliferation drug effects, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Female, HCT116 Cells, Humans, MCF-7 Cells, Mice, Models, Molecular, Molecular Structure, Neoplasms, Experimental drug therapy, Neoplasms, Experimental pathology, Protein Kinase Inhibitors chemical synthesis, Protein Kinase Inhibitors chemistry, Pyridazines chemical synthesis, Pyridazines chemistry, Receptors, Vascular Endothelial Growth Factor antagonists & inhibitors, Receptors, Vascular Endothelial Growth Factor metabolism, Structure-Activity Relationship, Antineoplastic Agents chemical synthesis, Antineoplastic Agents pharmacology, Drug Design, Protein Kinase Inhibitors pharmacology, Pyridazines pharmacology
Abstract

Certain pyridazine containing compounds 2a-f, 3a, b, 4a, b, 5a, b, 6a and b were synthesized and characterized by spectroscopic means and elemental analysis. All the synthesized compounds were screened for their cytotoxic activity in vitro on colon cancer cell line (HCT-116) and breast cancer cell line (MCF-7). In addition, the antitumor activity of the synthesized compounds was tested in vivo against Ehrlich's ascites carcinoma (EAC) solid tumor grown in mice. The in vitro vascular endothelial growth factor receptor (VEGFR) enzyme inhibition assay was carried out for the most active compounds at a single dose of 10 µM. The obtained results revealed that compound 5b, which showed potent cytotoxic activity against HCT-116 also, exhibited the highest inhibition in the VEGFR kinase assay (92.2%).

Published
2017
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3. Design, synthesis and screening of benzimidazole containing compounds with methoxylated aryl radicals as cytotoxic molecules on (HCT-116) colon cancer cells

Author

M. Mohsen Ismail, Elmeligie Salwa, Manal Mohammed, Mohammed K. Abdelhameid, and Ryad M. Noha

Subjects
Radiation-Sensitizing Agents, Benzimidazole, Antineoplastic Agents, Apoptosis, Caspase 3, 01 natural sciences, 03 medical and health sciences, chemistry.chemical_compound, Chromosomal Instability, Drug Discovery, medicine, Humans, Cytotoxic T cell, 030304 developmental biology, Pharmacology, chemistry.chemical_classification, 0303 health sciences, biology, 010405 organic chemistry, Aryl, Topoisomerase, Organic Chemistry, General Medicine, HCT116 Cells, Tubulin Modulators, 0104 chemical sciences, Podophyllotoxin, Enzyme, chemistry, Biochemistry, Drug Design, Colonic Neoplasms, biology.protein, Benzimidazoles, Drug Screening Assays, Antitumor, Camptothecin, medicine.drug
Abstract

A novel series of benzimidazole derivatives with methoxylated aryl groups was designed and synthesized as molecules with potential cytotoxic activity. In vitro cytotoxic activity over HCT-116 cells showed that N-(benzimidazothiazolone)acetamides 11a, 11b and 11c were found to be the most cytotoxic compounds compared camptothecin (CPT). The tested compounds had a dual topoisomerase I-β (Topo I-β) and tubulin inhibiting activities when compared to CPT and Podophyllotoxin (Podo) where, compounds l0a, l0b, 11a and 11b exhibited a potent inhibitory activity on Topo I-β enzyme in nano-molar concentration, on the other hand, compounds 12b and 13b exhibited the best inhibitory activity β-tubulin polymerization. Results of the cell cycle analysis as well as the results of annexin-V on HCT-116 cells showed that benzimidazothiazoles 12b and 13b had a pro-apoptotic activity higher than CPT by 1.33- and 1.30-folds, respectively. Moreover, the concentration of p53, Bax/Bcl-2 ratio and caspase 3/7 increased in compounds l0b, 11b, l2b, 13b, especially, compounds 11b and 13b exhibited an increased level of these mediators than CPT. Finally, compound 11b regulated the radiosensitizing activity of the HCT-116 cells by modulating the chromosomal instability.

Published
2021

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