الفهرس 
Cancer
Adenosine deaminase (ADA) deficiencyOnly 14 pages are availabe for public view
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Abstract
Cancer is a major burden of disease worldwide. Chemotherapy is one of the most powerful tools to treat cancer, and research continues to find new chemotherapy drugs. Newer types of drugs are being developed to work in different ways to attack cancer cells with low side effects. This study involves four transition metal complexes based on the Schiff base. The ligand and its metal complexes have been prepared and characterized by the aid of elemental and thermal analyses, spectra (FT‐IR, 1H NMR, MS, UV‐Vis, ESR, X‐ray powder diffraction), molar conductance and magnetic moment measurements. The XRD results unambiguously confirmed the nanosized particles of the complexes. This study aims to evaluate their antioxidant and antitumor activity through inhibition of Adenosine deaminase and Impacting their cytotoxic effect on different cell lines including cancer and normal cell lines then, the most affected one was chosen to study the expected mechanism of action of these compounds by determining the phase of cell cycle arrest. Their ability to inhibit ADA and obstruct DNA synthesis were evaluated and TOP1 level was measured, in addition to antioxidant, apoptotic, inflammatory, autophagic biomarkers. The study included: • The antioxidant activity of H2L and its metal complexes was determined by DPPH radical scavenging assay with Lascorbic acid as reference. • The cytotoxicity of H2L and its metal complexes was evaluated in vitro against human cancer cells including liver cancer cells (HepG2), breast cancer cells (MCF-7), and colorectal cancer cells (Caco2), in addition to normal human liver cells (THLE- 2) using MTT assay. The cytotoxicity of cisplatin (Cis), was used as reference of anticancer drug after 24 and 48 h. • selecting HepG2 cells as the most affected was chosen to study the mechanism of action. • Flow cytometric cell cycle analysis for HepG2 cells was performed after 24 and 48 h to detect the phase of cell cycle arrest. • The oxidative stress of H2L and its metal complexes was assessed by measuring GSH concentration and SOD activity in HepG2 cells. • The effect of H2L and its metal complexes on DNA synthesis was evaluated by their ability to inhibit ADA using molecular docking and by measuring ADA activity in HepG2 cells treated with their IC50 concentration for 24 and 48 h. • TOP Ι level was assessed as biomarker for DNA synthesis. • Their effect on different pathways was detrmined by measuring Bax as apoptotic, Bcl-2 as anti-apoptotic, IL-B1, as inflammatory and Beclin-1 as autophagic biomarkers in HepG2 cells treated with IC50 concentration of H2L and its metal complexes for 24 and 48 h using real time PCR. • Bax and Bcl-2 biomarkers were confirmed at protein level with western blot for HepG2 cells treated with Cu complex for 48 h as it gave the best results at gene level. The results indicated that: • H2L and its complexes metal have antioxidant activity. Cu and Co complexes showed high antioxidant activity with IC50 values of 3.7 , 4.0 μg/ml respectively • H2L and its metal complexes are safe against normal cells as their cytotoxicity appeared at high concentrations as almost IC50 values were >100μg/ml. • H2L and its metal complexes have cytotoxic activity against HepG2, MCF-7, and Caco2. The most cytotoxic effect was observed in HepG2 treated with H2L and Cu complex after 48 h of incubation with IC50 (2.21, 2.01) respectively. • H2L and its metal complexes induced cell-cycle arrest at G2/M phase. • GSH level and SOD activity were elevated in HepG2 cells treated with H2L and its metal complexes. • H2L and its metal complexes inhibited ADA, impeded DNA synthesis and TOP Ι level was decreased in treated HepG2. • H2L and its metal complexes induced apoptosis through up regulation of apoptotic gene Bax and down regulation of anti apoptotic gene Bcl-2. • Non-significant changes were observed in the relative expression of Beclin-1 and IL-B1 in HepG2 cells treated with H2L and its metal complexes. • Cu complex has a great potential to be developed to target liver cancer cells.