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Abstract
Cancer has proven to be one of the most intractable diseases to which humans are subjected. Cancer chemotherapy play an important role in the treatment of cancer. It has entered a new era of molecular targeted therapeutics, which is highly selective and not associated with the serious toxicities of conventional cytotoxic drugs. Unfortunately, targeted chemotherapy still has some limitations. The chief among them is the potential of cells to develp resistance. As a result, in most cases, it is advantageous to use them in combination, either with other targeted therapy or with traditional therapy. One of the most critical therapeutic target in the treatment of cancer is mutated BRAF kinase enzyme (V600EBRAF), which is involved in approximately 30% of human cancers.The present study was constructed to design and synthesize 42 pyridopyrazinone derivatives in order to investigate their activities against different cancer cell lines in addition, to study the possible interaction with the active site of mutated BRAF kinase enzyme. The 42 pyridopyrazinone derivatives were synthesized according to reported methods and their structures were elucidated using spectral analysis such as IR, 1HNMR and Mass spectroscopy in addition to elemental analysis. The in vitro antitumor screening was evaluated for the synthesized compounds against different cell lines such as melanoma, ovarian, thyroid and colon cancer using MTT assay method for 25 compounds and SRB assay method for 17 compound using sorafenib and doxorubicin as standards, respectivily. The results revealed that some of these compounds have a promising activity against thyroid and colon cancer