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

A new series of bis-chalcones 5-10 has been prepared using the condensation reaction of one equivalent of bis(acetophenones) 3a-f with two equivalents of 1,3-diphenyl-1H-pyrazole-4-carbaldehyde 4. Compounds 5-10 have been tested as for their anticancer activities in different human cancer cell lines in vitro, namely A431, A549, PC3, and the normal human skin fibroblast BJ1. Compounds 5 and 9 were found to be the most promising compounds in the prepared series with IC50 (50.3 and 50.1 og/ml, respectively) against epidermoid cancer cell line A431 compared to doxorubicin as reference drug. To decipher the mechanism of action exerted by the new compounds, the effect of compound 9 on the DNA damage in A431 and A549 cells was investigated.Compound 9 was investigated theoretically to different domain sets (4kmn, 2c6o, 2w3t, 4wt2, and 1dls). They illustrated different modes of action with different binding energies (-23.03, -27.14, -26.03, -21.19 and -33.12 Kcal/mol, respectively), in comparison with the binding readings of co-crystallized standard ligands (-15.13, -26.73, -18.20, -14.40 and -41.30 Kcal/mol), respectively. The most efficient binding mode was found with the apoptotic inhibitor IAP (4KMN), while it had only moderate affinities with the DHFR (1dls domain)

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