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العنوان
Study of the Mechanisms of Cancer Cells Death by Some New Transition Metal Complexes /
الناشر
Marwa Ebrahim Mohamed Elafify,
المؤلف
Elafify, Marwa Ebrahim Mohamed.
هيئة الاعداد
باحث / MMaarrwwaa EEbbrraahhiimm MMoohhaammeedd EEllaaffiiffy
مشرف / EL Shahat A. Toson
مشرف / Ahmed M. El-Hendawy
مشرف / ThanaaI. Shalaby
الموضوع
Biochemistry. Cancer.
تاريخ النشر
2020.
عدد الصفحات
347 p. :
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
Biochemistry
تاريخ الإجازة
10/2/2021
مكان الإجازة
جامعة دمياط - كلية العلوم - الكيمياء
الفهرس
Only 14 pages are availabe for public view

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Abstract

New V(IV), Mo(VI), and Ru(II) complexes containing the ligand 2,4-dihydroxyacetophenone-S-methyl dithiocarbazate (H2dhasm); [VO (dhasm)(bpy)] (1) (bpy = 2,20-bipyridine), [VO(dhasm)(phen)] (2) (phen = 1,10-phenanthroline), [MoO2(dhasm)(imz)] (3) (imz = imidazole), [MoO2(dhasm)(DMSO)] (4) (DMSO = dimethylsulfoxide), and [Ru(CO) (PPh3)2(dhasm)] (5) have been synthesized. The ligand and its complexes were structurally characterized by elemental analyses, IR, 1H NMR, EPR, ultraviolet (UV)–visible spectroscopies, magnetic susceptibility, and cyclic voltammetry measurements. Single crystal X-ray crystallography was used to establish the structure detail of (3) and (4) complexes confirming that the ligand coordinate to the metal ion in a bi-negative tridentate fashion (dhasm2−, ONS-donor) in a distorted octahedral geometry. The interaction with calf thymus DNA (CT DNA) and bovine serum albumin (BSA) of all compounds was studied by UV– visible and fluorescence spectroscopies. Both studies confirmed that these compounds bind to CTDNA and BSA through intercalation mode. The DNA and BSA cleavage activities of the complexes was also studied by using gel electrophoresis, and the results revealed that only complexes (2) and (5) have superior cleavage activity toward DNA in the presence of H2O2 and also have ability to photo induced protein cleavage. The cytotoxic activity (in vitro) of the complexes on three human cancer cell lines; human liver hepatocellular carcinoma (HepG2), breast adenocarcinoma (MCF7), and epitheliod carcinoma (Hela); and a normal human lung fibroblast (WI-38) was studied using MTT assay. The complexes exhibited a strong cytotoxicity effect compared with their parent ligand. The ruthenium (II) complex (5) showed the most potent growth inhibition of cancer cells. The complexes were also screened for their antioxidant, hemolytic, anti-hemolytic, anti-inflammatory as well as antibacterial activities. Moreover, the capabilities of complexes (2) and (5) to inhibit the growth of the tumor in mice bearing Ehrlich Ascites cells carcinoma are tested in vivo. Also, the mechanism of the apoptotic death in HepG2 cells was studied by observing an increased gene expression of caspase-3, BAX, P53 and decreased Bcl2 gene expression.