الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. Cancer can be treated by chemotherapy, radiation or hormonal therapy. Microtubules, globular protein, has a critical role in mitotic divisions. So that any disruption in its dynamics can result in apoptosis. Therefore, tubulin is considered an important target for many drugs in cancer therapy. Combretastatin A-4 (CA-4) is naturally occurring tubulin inhibitor. A wide variety of CA-4 analogues with potential antitubulin activity is known in literature. The present study involves design and synthesis of novel heterocyclic analogs of CA-4 in order to find more efficient and safe anticancer agents with fewer side effects. All of the synthetic compounds gave satisfactory analytical and spectroscopic data, which were in full accordance with their depicted structures. All the newly synthesized compounds were tested against a panel of four human cancer cell lines; MCF-7 (breast adenocarcinoma), HCT-116 (colon cancer), Hela (Epithelioid Carcinoma) and PC3 (Human prostate cancer) using CA-4 as a positive control. All compounds showed cytotoxic activity. Compounds 110b, 121, 122 and 125 showed potent antiproliferative activities almost the same activity of CA-4 with IC50 ranging from 6.9 to 13.7 μM. Docking simulation was performed with the crystal structure of tubulin using a potent tubulin inhibitor, CA-4, as lead molecule. This thesis consists of 105 pages including 5 tables, 35 figures, 177 references and ends with an Arabic summary.