Thesis (M.Sc.) - Cairo University - Faculty of Science - Department of Biochemistry

Novel bis (1,4-dihydropyridine) derivatives linked to aliphatic or aromatic core via ester as well as ether linkages7-16 were prepared, and confirmed by several spectral tools. The prepared compounds showed better cytotoxicity results against A549 than MCF7. The computational studies showed that compound 9 is binding to xIAP and cIAP1 with good energy score. With respect to the antibacterial activity, compound 14 exhibit the most efficiency one against the studied bacterial strains and hence it is used in the docking study on Ý-ketoacyl-ACP synthaseIII (fabH). The results showed good interaction of compound 14 with fabH. Four compounds were chosen for molecular studies on A549 cell line. The molecular data showed that all compounds caused cell cycle arrest at G1 phase and slightly increased the percentage of early apoptosis with no detectable DNA ladder characteristic of apoptotic cell death. The four compounds induced the up regulation of Bax gene and the down regulation of P53and Bcl2 genes. The activity of caspase 3 was slightly higher than control for compounds 10 and 16 and slightly lower than control for compounds 11 and 15. We also studied the effect of compound 11 on normal cell line (HFB4) after it's treatment with genotoxic factor (H₂ O₂) and we noticed that compound 11 reduces DNA damaging effect of H₂ O₂. So, the new compounds have limited side effects on normal cells and could be used as complementary drugs to reduce the harmful effects of other chemotherapeutic agent

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